Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of ...Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of the forced expiratory curve(FEF25%–75%),percentage of eosinophil,concentrations of eosinophil cationic protein(ECP)and interleukin(IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone.Subsequently,acute exacerbations were compared between two groups during the 24-week follow-up period.Results FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone.Meanwhile,the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone.Additionally,the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations,presumably secondary to reduction in airway inflammation.展开更多
Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment gr...Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment group,each group with 10 rats.The CVA model was induced by intraperitoneal injection combined with aerosolized ovalbumin(OVA),the treatment group was given 100 mg/ml of vitaminD330 minutes before challenge by administered orally.Airway hyperreaction were measured by airway resistance after inhalation of acetylcholine(Ach).Wright-Gimsa staining was used to observe the inflammatory cells in bronchoalveolar lavage fluid(BALF).HE and PAS were used to observe the morphological changes of lung tissue.OPN expression was detected by immunohistochemistry.Results:1)Airway hyperreaction:airway resistance after inhalation Ach in model group and treatment group were significantly higher than that in blank group(P<0.01),airway resistance in treatment group were lower than that in model group(P<0.01);2)Classification of inflammatory cells:The percentage of macrophages,lymphocytes,neutrophils,and eosinophils in the BALF of the model group and the treatment group were increased compared with the blank group(P<0.01),furthermore,the number of treatment group were lower than the model group(P<0.05);3)Morphological changes of lung tissue:a large amount of inflammatory cells and goblet cell proliferation were observed in the lung tissue of the model group,and these changes were slight in treatment group compared with model group;OPN expression in lung tissue:The expression of OPN in model and treatment group were increased compared with blank group(P<0.05),and the treatment group was lower than that of model group(P<0.05).The OPN content was positively correlated with the percentage of inflammatory cells in BALF(P<0.05).Conclusions:Vitamin D3 can reduce airway hyperreaction and airway inflammation in CVA rats.The mechanism may be related to the intervention of OPN expression in lung tissue.展开更多
Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided ...Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.展开更多
Objective To evaluate the effect of diisononyl phthalate(DINP) exposure during gestation and lactation on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. Methods Femal...Objective To evaluate the effect of diisononyl phthalate(DINP) exposure during gestation and lactation on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. Methods Female Wistar rats were treated with DINP at different dosages(0, 5, 50, and 500 mg/kg of body weight per day). The pups were sensitized and challenged by ovalbumin(OVA). The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin(HE) staining; and the relative cytokines in phosphoinositide 3-kinase(PI3K)/Akt pathway were measured by enzyme-linked immunosorbent assay(ELISA) and western blot analysis. Results There was no significant difference in DINP's effect on airway hyperresponsiveness(AHR) between male pups and female pups. In the 50 mg/(kg·d) DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance(RI) compared with those from controls(P<0.05). Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/(kg·d) DINP-treated group. However, in the 5 and 500 mg/(kg·d) DINP-treated pups, no significant effects were observed. Conclusion There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.展开更多
Objective: To investigate the influence of Danshen Injection on airway inflammation and CD4+CD25+ regulatory T cells(CD4+CD25+ Tr) of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatm...Objective: To investigate the influence of Danshen Injection on airway inflammation and CD4+CD25+ regulatory T cells(CD4+CD25+ Tr) of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods: 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids(BALF) were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain(HE). Flow cytometry was used to detect the CD4+CD25+ Tr ratio in peripheral blood mononuclear cells(PBMCs). Results: Total cell, the percentage of lymphocytes, neutrophils and eosinophils(Eos) in BALF of Danshen Injection-treated group were lower than that in asthma group(P ﹤ 0.05, P ﹤ 0.01). Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4+CD25+ Tr of asthma group was lower than that of control and Danshen Injection treated group (P ﹤ 0.05). Conclusion: Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4+CD25+ Tr.展开更多
OBJECTIVE To develop an in vitro airway epithelial cell model suitable for the large-scale studies of compounds that can suppress lipopolysaccharide(LPS)-and tumor necrosis factor alpha(TNFα)-induced airway inflammat...OBJECTIVE To develop an in vitro airway epithelial cell model suitable for the large-scale studies of compounds that can suppress lipopolysaccharide(LPS)-and tumor necrosis factor alpha(TNFα)-induced airway inflammation.METHODS We have optimized the protocols to culture BEAS-2B,a normal human bronchial epithelial cell line,in glass-bottom 384-well microtiter plates.The cells were stimulated with TNFαand LPS from Pseudomonas aeruginosa,a common lunginfection pathogen in cystic fibrosis and chronic obstructive pulmonary disease.We used ELISA to measure the secretion levels of two pro-inflammatory cytokines,interleukin(IL)-6and-8,after 0,4,8,16,24 hof stimulation;and immunofluorescence microscopy to measure the nuclear translocation of RelA,a subunit of the NF-κB complex,after 0,15,30,60,120 min of stimulation.To suppress the inflammatory response,we pre-treated the cells with a specific IκB kinase-2inhibitor,TPCA-1;the main bioactive component of Andrographis paniculata,andrographolide;and DMSO control for 1h.RESULTS We found that individual stimulant(either TNFα10ng·mL-1 or LPS 10μg·mL-1)increased the IL-6and IL-8 secretion levels by^12-17 foldsas compared to DMSO controls after 8h of stimulation.The combined stimulation(10ng·mL-1 TNFαand 10μg·mL-1 LPS)induced even higher IL-6 and -8 levels(~18-21 folds)at the same time points.Importantly,our imaging study shows that the NF-κB activation is early but transient under TNFαstimulation,late but sustained under LPS stimulation,and early and sustained under the combined stimulation.Finally,we also found that TPCA-1 10μmol·L-1 or andrographolide 30μmol·L-1 drastically reduced the IL-6 and -8 levels down to 4.5-9 folds as compared to the controls.CONCLUSIONThe combined TNFαand LPS stimulations induce faster and more sustained inflammatory responses,which can still be suppressed by anti-inflammatory compounds in our cell model.These more comprehensive activations of inflammatory signaling pathways will enable us to study and distinguish the mechanisms of different anti-inflammatory compounds or natural products.展开更多
Summary: The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-κB) were explored. Thirty-two S...Summary: The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-κB) were explored. Thirty-two SD rats were randomly divided into 4 groups: control group, asthma group, dexamethasone treatment group and retinotic acid treatment group. The total and differential cell counts in the collected bronchoalveolar lavage fluid (BALF) were measured. The pathological changes in lung tissues were estimated by scoring. The expression of NF-κB inhibitor (IκBa), NF-κB, intercellular adhering molecule-1 (ICAM-1) in lung tissue was detected by immunohistochemical method. The results showed that in the two treatment groups, the total cell counts and proportion of inflammatory cells in BALF were significantly reduced, but there was no significant difference in differential cell counts in BALF between them. The pathological changes in lung tissues in the treatment groups were significantly attenuated as compared with asthma group. Except the epithelial injury in retinotic acid treatment group was milder than in dexamethasone treatment group, the remaining lesions showed no significant difference between them. In the two treatment groups, the expression of IκBa was increased, while the expression of NF-κB and ICAM-1 decreased with the difference between the two groups being not significant. It was concluded that the similar anti-inflammatory effects and mechanism of ATRA on airway in asthmatic rats to those of dexamethasone were contributed to the increase of cytoplasmic IκBa content and suppression of NF-κB activation and expression.展开更多
Aim: To explore the effects of Baicalin and Ligustrazine on airway inflammation and construction and underlying mechanisms through the expressions of GATA-3, IL-5, MMP-9 and TIMP-1 in asthmatic rats. Methods: 30 Wista...Aim: To explore the effects of Baicalin and Ligustrazine on airway inflammation and construction and underlying mechanisms through the expressions of GATA-3, IL-5, MMP-9 and TIMP-1 in asthmatic rats. Methods: 30 Wistar rats were randomly divided equally into five groups. Lung tissues were sliced. WBC and Eos in lung tissue were estimated by HE stain and the expressions of IL-5, GATA-3, MMP-9, TIMP-1 and collagen type IV in lung tissue were observed by immunohistochemistry. The airway wall and airway smooth muscle thicknesses were measured by computed image analysis system. Results: Compared with asthma group, EOS counts and the expression of IL-5 and GATA-3 in the lung tissue were significantly lower in normal controlled groups (P Baicalin or Ligustrazine, EOS decreased, and the thicknesses of airway wall and airway smooth muscle became thinner compared with asthma group. Meanwhile, the expression of collagen type IV, IL-5, GATA-3, MMP-9 and TIMP-1 significantly decreased (P < 0.05). Airway wall thickness and collagen type Ⅳ were associated with Eos, IL-5, TAGA-3, MMP-9, TIMP-1 and MMP-9/ TIMP-1. Conclusion: Two herbs could diminish infiltration of EOS with inhibiting the expressions of IL-5, and GATA-3, meanwhile, decrease the deposition of collagen type IV and the thickness of the airway smooth muscle through regulating MMP-9, TIMP-1 level and the balance between MMP-9 and TIMP-1, additionally, had synergetic effects.展开更多
Objective To establish allergic airway inflammation model in late-phase airwayreaction of Sprague-Dawley (SD) rats. Methods Thirty-six SD rats were randomly divided intothree groups: control group (Group Ⅰ),single ch...Objective To establish allergic airway inflammation model in late-phase airwayreaction of Sprague-Dawley (SD) rats. Methods Thirty-six SD rats were randomly divided intothree groups: control group (Group Ⅰ),single challenge group (Group Ⅱ),consecutive challenge group(Group Ⅲ). The rats in Group Ⅱ and Group Ⅲ were sensitized twice by injection of ovalbumin (OA) to-gether with aluminum hydroxide and Bordetella pertussis as adjuvants, followed by challenge withaerosolized OA for 20 min once in Group Ⅱ or one time on each day for one week in Group Ⅲ . Therats in Group Ⅰ received 0.9 % saline by injection and inhalation. Results Conpared uith groupⅠ , there were positive symptoms observed in the group Ⅱ and group Ⅲ; the amount of total leucocytesand eosinophil percentage in brochoalveolar lauage fluid (BALF) significantly increased (P＜0.05 orP ＜0.01 respectively) in Group Ⅱ or Ⅲ; histopathologic changes of lung showed acute allergic inflam-mation changes in Group Ⅱ : Disrupted epithelium damaged subepithelial structure and eosinophil infiltra-tion the in the airway wall. As for the Group Ⅲ , there were allergen-induced characteristic features ofchronic allergic airways inflammation: hypertrophy and hyperplasia of bronchial smooth muscle, gobletcell hyperplasia , basement membrane thickening, eosinophil infiltration, edema. Conclusion The mod-el of allergic airway inflammation in late-phase response of SD rats was successfully established by OAsensitization (twice) and consecutive challenge.展开更多
Objective:To study the effect of anxiety and depression on pulmonary function as well as airway inflammation and remodeling in patients with bronchial asthma.Methods: A total of 118 adult patients with bronchial asthm...Objective:To study the effect of anxiety and depression on pulmonary function as well as airway inflammation and remodeling in patients with bronchial asthma.Methods: A total of 118 adult patients with bronchial asthma who were treated in our hospital between September 2015 and January 2017 were divided into pure depression group (n=30), pure anxiety group (n=47), depression + anxiety group (n=19) and mental health group (n=22) according to the Self-Rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) score. The differences in the levels of pulmonary function parameters as well as the contents of serum inflammatory factors and airway remodeling indexes were compared among the four groups. Results: FEV1, PEF and FVC levels as well as serum TIMP-1 contents of pure depression group, pure anxiety group and depression + anxiety group were lower than those of mental health group while serum IL-2, IL-4, IL-8, IL-33, VEGF, OPN, TGF-β1 and MMP-9 contents were higher than those of mental health group, and FEV1, PEF and FVC levels as well as serum TIMP-1 content of depression + anxiety group were lower than those of pure depression group and pure anxiety group while serum IL-2, IL-4, IL-8, IL-33, VEGF, OPN, TGF-β1 and MMP-9 contents were higher than those of pure depression group and pure anxiety group. Conclusion: Anxiety and depression can aggravate the pulmonary function injury, increase airway inflammation and promote airway remodeling process in patients with bronchial asthma.展开更多
Objective To confirm if pulmonary epithelial cells express Toll-like receptor 4 (TLR4) and investigate the role of TLR4 in airway inflammation of chronic obstructive pulmonary diseases (COPD). MethodsThe expressions o...Objective To confirm if pulmonary epithelial cells express Toll-like receptor 4 (TLR4) and investigate the role of TLR4 in airway inflammation of chronic obstructive pulmonary diseases (COPD). MethodsThe expressions of TLR4, IL-8 mRNA and NF-κB activation stimulated by differen factors [lipopolysacharides (LPS), interleukin-1β, cigarette smoking extract (CSE)] in pulmonary epithelial cells were investigated.Results LPS, CSE and IL-1β induced the production of IL-8 and activation of NF-κB. The levels of IL-8 mRNA and NF-κB protein in E1A+ cell were markedly higher than E1A- cell and A549 cell (P<0.05). The TLR4 mRNA of all the cells increased along with the increase of LPS’ stimulated time. There was significant difference among different LPS’ doses (12 h: P=0.039; 24 h: P=0.013). The TLR4 mRNA of E1A+ cell was higher than the other two groups (P<0.05). IL-1β induced all the cells expressing TLR4 mRNA. CSE had no effect on the expression of TLR4 mRNA. Conclusion Pulmonary epithelial cells express TLR4. LPS and IL-1β up-regulate IL-8 mediated via the activation of NF-κB induced by TLR4. But CSE up-regulates IL-8 mediated via the activation of NF-κB, which has no relation to TLR4 and may have another signal transduction pathway.展开更多
Objective:To study the correlation of interleukin-6 (IL-6) 572C/G gene polymorphism with airway inflammation and remodeling in patients with COPD.Methods: Patients with stable COPD who were treated in Hanzhong Central...Objective:To study the correlation of interleukin-6 (IL-6) 572C/G gene polymorphism with airway inflammation and remodeling in patients with COPD.Methods: Patients with stable COPD who were treated in Hanzhong Central Hospital between March 2015 and December 2017 were selected and enrolled in the COPD group of the study, and healthy volunteers who received physical examination in Hanzhong Central Hospital during the same period and had general information matched with that of patients with COPD were selected as the control group. The peripheral blood was collected to detect the IL-6 gene 572 C/G locus polymorphism, and the serum was collected to detect the levels of inflammatory response mediators and airway remodeling indexes.Results:The proportion of GG genotype in COPD group was higher than that in control group, and the proportion of GC+CC genotype was lower than that in control group;serum IL-6, IL-21, IFN-γ, CXCL13, CTRP4, CTRP5, TGF-β1, VEGF, MMP2 and NE levels of COPD group were significantly higher than those of control group whereas 1-AT and TIMP1 levels were significantly lower than those of control group, and serum IL-6, IL-21, IFN-γ, CXCL13, CTRP4, CTRP5, TGF-β1, VEGF, MMP2 and NE levels of COPD patients with GG genotype were higher than those of COPD patients with GC+CC genotype whereas 1-AT and TIMP1 levels were lower than those of COPD patients with GC+CC genotype.Conclusion:The mutation from IL-6 gene 572C/G locus allele C to G can aggravate the inflammatory response and airway remodeling in the course of COPD.展开更多
There are some errors in the article“Electroacupunctureinduced activation of GABAergic system alleviates airway inflammation in asthma model by suppressing TLR4/MyD88/NF-kB signaling pathway”which appeared in vol.13...There are some errors in the article“Electroacupunctureinduced activation of GABAergic system alleviates airway inflammation in asthma model by suppressing TLR4/MyD88/NF-kB signaling pathway”which appeared in vol.136,issue 4,page 451–460 of Chinese Medical Journal.展开更多
Allergic asthma reflects an imbalance of pro-and anti-inflammatory components of the immune system,and in asthma patients,endogenous mechanisms that maintain homeostasis in the lung are thought to be defective.IL-10 i...Allergic asthma reflects an imbalance of pro-and anti-inflammatory components of the immune system,and in asthma patients,endogenous mechanisms that maintain homeostasis in the lung are thought to be defective.IL-10 is recognized as an important anti-inflammatory cytokine that suppresses the activity of many innate and adaptive immune cells.Genomic variants in the IL10 locus are associated with increased asthma prevalence in adults,and patients with severe asthma are more likely to have the low IL-10-producing haplotype[3].Accordingly,compared with healthy controls,patients with asthma were reported to have reduced IL-10 levels in bronchoalveolar lavage(BAL)fluid and alveolar macrophages[4].Other groups,however,observed increased or unchanged levels of IL-10 in patients[5,6].The anti-inflammatory function of IL-10 was demonstrated in various mouse models in which eosinophilic airway inflammation was inhibited by exogenous IL-10 and enhanced by IL-10 deficiency[6].In HDM-driven airway inflammation models,IL-10 was shown to exert direct effects on Th2 cells and to improve the balance between regulatory T cells and Th17 cells[7,8].However,it was also reported that IL-10 does not affect eosinophilic inflammation and that IL-10 could promote allergen-induced airway hyperresponsiveness[9,10].Therefore,it can be concluded that data on the role of IL-10 in asthma are rather contradictory,which is likely caused by the nature of the allergen used,allergen dose,and the protocols of sensitization and challenge.The fact that IL-10 is produced by almost every cell type of the immune system makes it even more challenging to unravel its role in allergic airway inflammation.In this issue of Cell.Mol.Immunol.,Qian et al.report a remarkable pro-inflammatory role of B cell-derived IL-10[11].They employ mice that are deficient in Bcl-3,a regulator of NF-κB that was previously linked to the regulation of Il10 gene expression in T lymphocytes[12].In contrast to classical,cytoplasmic IκB family inhibitors,Bcl-3 is present in the nucleus and modulates NF-κB-mediated gene expression by directly contacting NF-κB p50.Qian et al.observed that IL-10 production was elevated in the lungs of Bcl-3−/−mice subjected to HDM-induced allergic airway inflammation compared with Bcl-3+/+mice.Significantly increased infiltration of eosinophils and lymphocytes was found in the BAL fluid of Bcl-3-deficient mice.The levels of the type 2 cytokines IL-4,IL-5,and IL-13 in the lungs and in HDM-restimulated MLN cell cultures were higher in the absence of Bcl-3.Importantly,Bcl-3−/−mice showed considerably increased airway hyperreactivity in response to increasing doses of metacholine.These results support a model in which Bcl-3 protects against HDM-induced allergic asthma.展开更多
Objective To explore the effect of Yunpi Xiefei Huatan Decoction(YXHD)on airway inflammation and mucus hypersecretion in young asthmatic rats based on the correlation of interleukin(IL)-23/T helper cell(Th17)inflammat...Objective To explore the effect of Yunpi Xiefei Huatan Decoction(YXHD)on airway inflammation and mucus hypersecretion in young asthmatic rats based on the correlation of interleukin(IL)-23/T helper cell(Th17)inflammation axis and phosphatidylinositol 3kinase(PI3K)/protein kinase B(AKT)/nuclear factor kappa-B(NF-κB)signal axis.Methods Fifty-six young SD rats were randomly divided into 7 groups:normal group,model group,low-dose group of YXHD(LTCM)。展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
基金supported by the National Natural Science Foundation of China(No.81970024).
文摘Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of the forced expiratory curve(FEF25%–75%),percentage of eosinophil,concentrations of eosinophil cationic protein(ECP)and interleukin(IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone.Subsequently,acute exacerbations were compared between two groups during the 24-week follow-up period.Results FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone.Meanwhile,the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone.Additionally,the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations,presumably secondary to reduction in airway inflammation.
基金Sichuan provincial cadre health-care project(2017-1601)Nanchong municipal strategic cooperation projects in science and technology(18SXHZ0301,18SXHZ0300)
文摘Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment group,each group with 10 rats.The CVA model was induced by intraperitoneal injection combined with aerosolized ovalbumin(OVA),the treatment group was given 100 mg/ml of vitaminD330 minutes before challenge by administered orally.Airway hyperreaction were measured by airway resistance after inhalation of acetylcholine(Ach).Wright-Gimsa staining was used to observe the inflammatory cells in bronchoalveolar lavage fluid(BALF).HE and PAS were used to observe the morphological changes of lung tissue.OPN expression was detected by immunohistochemistry.Results:1)Airway hyperreaction:airway resistance after inhalation Ach in model group and treatment group were significantly higher than that in blank group(P<0.01),airway resistance in treatment group were lower than that in model group(P<0.01);2)Classification of inflammatory cells:The percentage of macrophages,lymphocytes,neutrophils,and eosinophils in the BALF of the model group and the treatment group were increased compared with the blank group(P<0.01),furthermore,the number of treatment group were lower than the model group(P<0.05);3)Morphological changes of lung tissue:a large amount of inflammatory cells and goblet cell proliferation were observed in the lung tissue of the model group,and these changes were slight in treatment group compared with model group;OPN expression in lung tissue:The expression of OPN in model and treatment group were increased compared with blank group(P<0.05),and the treatment group was lower than that of model group(P<0.05).The OPN content was positively correlated with the percentage of inflammatory cells in BALF(P<0.05).Conclusions:Vitamin D3 can reduce airway hyperreaction and airway inflammation in CVA rats.The mechanism may be related to the intervention of OPN expression in lung tissue.
基金Construction Project for Famous Doctors of Traditional Chinese Medicine of Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine(No.[2019]18)。
文摘Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.
基金financially supported by the Natural Science Foundation of China(Grant Number:81072263)Shanghai Natural Science Foundation(Grant Number:10ZR1402000)
文摘Objective To evaluate the effect of diisononyl phthalate(DINP) exposure during gestation and lactation on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. Methods Female Wistar rats were treated with DINP at different dosages(0, 5, 50, and 500 mg/kg of body weight per day). The pups were sensitized and challenged by ovalbumin(OVA). The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin(HE) staining; and the relative cytokines in phosphoinositide 3-kinase(PI3K)/Akt pathway were measured by enzyme-linked immunosorbent assay(ELISA) and western blot analysis. Results There was no significant difference in DINP's effect on airway hyperresponsiveness(AHR) between male pups and female pups. In the 50 mg/(kg·d) DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance(RI) compared with those from controls(P<0.05). Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/(kg·d) DINP-treated group. However, in the 5 and 500 mg/(kg·d) DINP-treated pups, no significant effects were observed. Conclusion There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.
基金This This work was supported by a grant from the Science and Technology Foundation of Hubei Province (2003AA301C10)
文摘Objective: To investigate the influence of Danshen Injection on airway inflammation and CD4+CD25+ regulatory T cells(CD4+CD25+ Tr) of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods: 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids(BALF) were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain(HE). Flow cytometry was used to detect the CD4+CD25+ Tr ratio in peripheral blood mononuclear cells(PBMCs). Results: Total cell, the percentage of lymphocytes, neutrophils and eosinophils(Eos) in BALF of Danshen Injection-treated group were lower than that in asthma group(P ﹤ 0.05, P ﹤ 0.01). Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4+CD25+ Tr of asthma group was lower than that of control and Danshen Injection treated group (P ﹤ 0.05). Conclusion: Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4+CD25+ Tr.
基金Acknowledgments We thank ProfYongjun Liu, Dangsheng Li and Yangxin Fu for helpful comments and Dr Sheri Skinner for reviewing the manuscript and for constructive suggestions. This work was supported by grants from the National Natural Science Foundation of China （30530700, 30623003, 30600568, 30721065, 90713044, 30600308, 30801011, 30870126） and CAS project （KSCX1-YW-R-43）, grant from SIBS project （2007KIP301）, grants from the Ministry of Science and Technology （2006CB504300, 2007CB512404, 2006AA02A247, 20072714）, the Technology Commission of Shanghai Municipality （88014199, 07DZ22916, 07XD14033, 064319034, 08431903004, 2008ZX10206, 08DZ2291703）, EU project （FP6-2005-SSP-5-B, SP5B-CT-2006-044161） and from the E-institutes of Shanghai Universities Immunology Division.
基金The project supported by National Medical Research Council Cooperative Basic Research Grant(CBRG11nov032)the Bioinformatics Institute,Biomedical Research Council,A*STAR,Singapore
文摘OBJECTIVE To develop an in vitro airway epithelial cell model suitable for the large-scale studies of compounds that can suppress lipopolysaccharide(LPS)-and tumor necrosis factor alpha(TNFα)-induced airway inflammation.METHODS We have optimized the protocols to culture BEAS-2B,a normal human bronchial epithelial cell line,in glass-bottom 384-well microtiter plates.The cells were stimulated with TNFαand LPS from Pseudomonas aeruginosa,a common lunginfection pathogen in cystic fibrosis and chronic obstructive pulmonary disease.We used ELISA to measure the secretion levels of two pro-inflammatory cytokines,interleukin(IL)-6and-8,after 0,4,8,16,24 hof stimulation;and immunofluorescence microscopy to measure the nuclear translocation of RelA,a subunit of the NF-κB complex,after 0,15,30,60,120 min of stimulation.To suppress the inflammatory response,we pre-treated the cells with a specific IκB kinase-2inhibitor,TPCA-1;the main bioactive component of Andrographis paniculata,andrographolide;and DMSO control for 1h.RESULTS We found that individual stimulant(either TNFα10ng·mL-1 or LPS 10μg·mL-1)increased the IL-6and IL-8 secretion levels by^12-17 foldsas compared to DMSO controls after 8h of stimulation.The combined stimulation(10ng·mL-1 TNFαand 10μg·mL-1 LPS)induced even higher IL-6 and -8 levels(~18-21 folds)at the same time points.Importantly,our imaging study shows that the NF-κB activation is early but transient under TNFαstimulation,late but sustained under LPS stimulation,and early and sustained under the combined stimulation.Finally,we also found that TPCA-1 10μmol·L-1 or andrographolide 30μmol·L-1 drastically reduced the IL-6 and -8 levels down to 4.5-9 folds as compared to the controls.CONCLUSIONThe combined TNFαand LPS stimulations induce faster and more sustained inflammatory responses,which can still be suppressed by anti-inflammatory compounds in our cell model.These more comprehensive activations of inflammatory signaling pathways will enable us to study and distinguish the mechanisms of different anti-inflammatory compounds or natural products.
文摘Summary: The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-κB) were explored. Thirty-two SD rats were randomly divided into 4 groups: control group, asthma group, dexamethasone treatment group and retinotic acid treatment group. The total and differential cell counts in the collected bronchoalveolar lavage fluid (BALF) were measured. The pathological changes in lung tissues were estimated by scoring. The expression of NF-κB inhibitor (IκBa), NF-κB, intercellular adhering molecule-1 (ICAM-1) in lung tissue was detected by immunohistochemical method. The results showed that in the two treatment groups, the total cell counts and proportion of inflammatory cells in BALF were significantly reduced, but there was no significant difference in differential cell counts in BALF between them. The pathological changes in lung tissues in the treatment groups were significantly attenuated as compared with asthma group. Except the epithelial injury in retinotic acid treatment group was milder than in dexamethasone treatment group, the remaining lesions showed no significant difference between them. In the two treatment groups, the expression of IκBa was increased, while the expression of NF-κB and ICAM-1 decreased with the difference between the two groups being not significant. It was concluded that the similar anti-inflammatory effects and mechanism of ATRA on airway in asthmatic rats to those of dexamethasone were contributed to the increase of cytoplasmic IκBa content and suppression of NF-κB activation and expression.
文摘Aim: To explore the effects of Baicalin and Ligustrazine on airway inflammation and construction and underlying mechanisms through the expressions of GATA-3, IL-5, MMP-9 and TIMP-1 in asthmatic rats. Methods: 30 Wistar rats were randomly divided equally into five groups. Lung tissues were sliced. WBC and Eos in lung tissue were estimated by HE stain and the expressions of IL-5, GATA-3, MMP-9, TIMP-1 and collagen type IV in lung tissue were observed by immunohistochemistry. The airway wall and airway smooth muscle thicknesses were measured by computed image analysis system. Results: Compared with asthma group, EOS counts and the expression of IL-5 and GATA-3 in the lung tissue were significantly lower in normal controlled groups (P Baicalin or Ligustrazine, EOS decreased, and the thicknesses of airway wall and airway smooth muscle became thinner compared with asthma group. Meanwhile, the expression of collagen type IV, IL-5, GATA-3, MMP-9 and TIMP-1 significantly decreased (P < 0.05). Airway wall thickness and collagen type Ⅳ were associated with Eos, IL-5, TAGA-3, MMP-9, TIMP-1 and MMP-9/ TIMP-1. Conclusion: Two herbs could diminish infiltration of EOS with inhibiting the expressions of IL-5, and GATA-3, meanwhile, decrease the deposition of collagen type IV and the thickness of the airway smooth muscle through regulating MMP-9, TIMP-1 level and the balance between MMP-9 and TIMP-1, additionally, had synergetic effects.
基金Supported by the Natural Science Foundation of Jiangsu Province(BK2001160)
文摘Objective To establish allergic airway inflammation model in late-phase airwayreaction of Sprague-Dawley (SD) rats. Methods Thirty-six SD rats were randomly divided intothree groups: control group (Group Ⅰ),single challenge group (Group Ⅱ),consecutive challenge group(Group Ⅲ). The rats in Group Ⅱ and Group Ⅲ were sensitized twice by injection of ovalbumin (OA) to-gether with aluminum hydroxide and Bordetella pertussis as adjuvants, followed by challenge withaerosolized OA for 20 min once in Group Ⅱ or one time on each day for one week in Group Ⅲ . Therats in Group Ⅰ received 0.9 % saline by injection and inhalation. Results Conpared uith groupⅠ , there were positive symptoms observed in the group Ⅱ and group Ⅲ; the amount of total leucocytesand eosinophil percentage in brochoalveolar lauage fluid (BALF) significantly increased (P＜0.05 orP ＜0.01 respectively) in Group Ⅱ or Ⅲ; histopathologic changes of lung showed acute allergic inflam-mation changes in Group Ⅱ : Disrupted epithelium damaged subepithelial structure and eosinophil infiltra-tion the in the airway wall. As for the Group Ⅲ , there were allergen-induced characteristic features ofchronic allergic airways inflammation: hypertrophy and hyperplasia of bronchial smooth muscle, gobletcell hyperplasia , basement membrane thickening, eosinophil infiltration, edema. Conclusion The mod-el of allergic airway inflammation in late-phase response of SD rats was successfully established by OAsensitization (twice) and consecutive challenge.
文摘Objective:To study the effect of anxiety and depression on pulmonary function as well as airway inflammation and remodeling in patients with bronchial asthma.Methods: A total of 118 adult patients with bronchial asthma who were treated in our hospital between September 2015 and January 2017 were divided into pure depression group (n=30), pure anxiety group (n=47), depression + anxiety group (n=19) and mental health group (n=22) according to the Self-Rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) score. The differences in the levels of pulmonary function parameters as well as the contents of serum inflammatory factors and airway remodeling indexes were compared among the four groups. Results: FEV1, PEF and FVC levels as well as serum TIMP-1 contents of pure depression group, pure anxiety group and depression + anxiety group were lower than those of mental health group while serum IL-2, IL-4, IL-8, IL-33, VEGF, OPN, TGF-β1 and MMP-9 contents were higher than those of mental health group, and FEV1, PEF and FVC levels as well as serum TIMP-1 content of depression + anxiety group were lower than those of pure depression group and pure anxiety group while serum IL-2, IL-4, IL-8, IL-33, VEGF, OPN, TGF-β1 and MMP-9 contents were higher than those of pure depression group and pure anxiety group. Conclusion: Anxiety and depression can aggravate the pulmonary function injury, increase airway inflammation and promote airway remodeling process in patients with bronchial asthma.
文摘Objective To confirm if pulmonary epithelial cells express Toll-like receptor 4 (TLR4) and investigate the role of TLR4 in airway inflammation of chronic obstructive pulmonary diseases (COPD). MethodsThe expressions of TLR4, IL-8 mRNA and NF-κB activation stimulated by differen factors [lipopolysacharides (LPS), interleukin-1β, cigarette smoking extract (CSE)] in pulmonary epithelial cells were investigated.Results LPS, CSE and IL-1β induced the production of IL-8 and activation of NF-κB. The levels of IL-8 mRNA and NF-κB protein in E1A+ cell were markedly higher than E1A- cell and A549 cell (P<0.05). The TLR4 mRNA of all the cells increased along with the increase of LPS’ stimulated time. There was significant difference among different LPS’ doses (12 h: P=0.039; 24 h: P=0.013). The TLR4 mRNA of E1A+ cell was higher than the other two groups (P<0.05). IL-1β induced all the cells expressing TLR4 mRNA. CSE had no effect on the expression of TLR4 mRNA. Conclusion Pulmonary epithelial cells express TLR4. LPS and IL-1β up-regulate IL-8 mediated via the activation of NF-κB induced by TLR4. But CSE up-regulates IL-8 mediated via the activation of NF-κB, which has no relation to TLR4 and may have another signal transduction pathway.
文摘Objective:To study the correlation of interleukin-6 (IL-6) 572C/G gene polymorphism with airway inflammation and remodeling in patients with COPD.Methods: Patients with stable COPD who were treated in Hanzhong Central Hospital between March 2015 and December 2017 were selected and enrolled in the COPD group of the study, and healthy volunteers who received physical examination in Hanzhong Central Hospital during the same period and had general information matched with that of patients with COPD were selected as the control group. The peripheral blood was collected to detect the IL-6 gene 572 C/G locus polymorphism, and the serum was collected to detect the levels of inflammatory response mediators and airway remodeling indexes.Results:The proportion of GG genotype in COPD group was higher than that in control group, and the proportion of GC+CC genotype was lower than that in control group;serum IL-6, IL-21, IFN-γ, CXCL13, CTRP4, CTRP5, TGF-β1, VEGF, MMP2 and NE levels of COPD group were significantly higher than those of control group whereas 1-AT and TIMP1 levels were significantly lower than those of control group, and serum IL-6, IL-21, IFN-γ, CXCL13, CTRP4, CTRP5, TGF-β1, VEGF, MMP2 and NE levels of COPD patients with GG genotype were higher than those of COPD patients with GC+CC genotype whereas 1-AT and TIMP1 levels were lower than those of COPD patients with GC+CC genotype.Conclusion:The mutation from IL-6 gene 572C/G locus allele C to G can aggravate the inflammatory response and airway remodeling in the course of COPD.
文摘There are some errors in the article“Electroacupunctureinduced activation of GABAergic system alleviates airway inflammation in asthma model by suppressing TLR4/MyD88/NF-kB signaling pathway”which appeared in vol.136,issue 4,page 451–460 of Chinese Medical Journal.
文摘Allergic asthma reflects an imbalance of pro-and anti-inflammatory components of the immune system,and in asthma patients,endogenous mechanisms that maintain homeostasis in the lung are thought to be defective.IL-10 is recognized as an important anti-inflammatory cytokine that suppresses the activity of many innate and adaptive immune cells.Genomic variants in the IL10 locus are associated with increased asthma prevalence in adults,and patients with severe asthma are more likely to have the low IL-10-producing haplotype[3].Accordingly,compared with healthy controls,patients with asthma were reported to have reduced IL-10 levels in bronchoalveolar lavage(BAL)fluid and alveolar macrophages[4].Other groups,however,observed increased or unchanged levels of IL-10 in patients[5,6].The anti-inflammatory function of IL-10 was demonstrated in various mouse models in which eosinophilic airway inflammation was inhibited by exogenous IL-10 and enhanced by IL-10 deficiency[6].In HDM-driven airway inflammation models,IL-10 was shown to exert direct effects on Th2 cells and to improve the balance between regulatory T cells and Th17 cells[7,8].However,it was also reported that IL-10 does not affect eosinophilic inflammation and that IL-10 could promote allergen-induced airway hyperresponsiveness[9,10].Therefore,it can be concluded that data on the role of IL-10 in asthma are rather contradictory,which is likely caused by the nature of the allergen used,allergen dose,and the protocols of sensitization and challenge.The fact that IL-10 is produced by almost every cell type of the immune system makes it even more challenging to unravel its role in allergic airway inflammation.In this issue of Cell.Mol.Immunol.,Qian et al.report a remarkable pro-inflammatory role of B cell-derived IL-10[11].They employ mice that are deficient in Bcl-3,a regulator of NF-κB that was previously linked to the regulation of Il10 gene expression in T lymphocytes[12].In contrast to classical,cytoplasmic IκB family inhibitors,Bcl-3 is present in the nucleus and modulates NF-κB-mediated gene expression by directly contacting NF-κB p50.Qian et al.observed that IL-10 production was elevated in the lungs of Bcl-3−/−mice subjected to HDM-induced allergic airway inflammation compared with Bcl-3+/+mice.Significantly increased infiltration of eosinophils and lymphocytes was found in the BAL fluid of Bcl-3-deficient mice.The levels of the type 2 cytokines IL-4,IL-5,and IL-13 in the lungs and in HDM-restimulated MLN cell cultures were higher in the absence of Bcl-3.Importantly,Bcl-3−/−mice showed considerably increased airway hyperreactivity in response to increasing doses of metacholine.These results support a model in which Bcl-3 protects against HDM-induced allergic asthma.
文摘Objective To explore the effect of Yunpi Xiefei Huatan Decoction(YXHD)on airway inflammation and mucus hypersecretion in young asthmatic rats based on the correlation of interleukin(IL)-23/T helper cell(Th17)inflammation axis and phosphatidylinositol 3kinase(PI3K)/protein kinase B(AKT)/nuclear factor kappa-B(NF-κB)signal axis.Methods Fifty-six young SD rats were randomly divided into 7 groups:normal group,model group,low-dose group of YXHD(LTCM)。
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
