[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were ran...[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were randomly divided into AMI-RI model control group and citrus pigment A/B/C groups(n=8).The naringenin A,B,and C groups were administrated 20,40 and 80 mg/(kg•d)for 10 d.The AMI group served as the negative control and was not treated.At the conclusion of the treatment regimen,a sample of intraventricular blood was collected for the purpose of measuring lactate dehydrogenase(LDH),glutathione peroxidase(GLH-PX),nitric oxide(NO),and superoxide dismutase(SOD)levels.Additionally,myocardial tissue was identified within the ischemic region.The content of malondialdehyde(MDA)was determined by inducing nitric oxide synthase(iNOS)and endodermal nitric oxide synthase(eNOS)positive cells in the left anterior descending coronary artery.[Results]Following citrus treatment,the contents of GLH-PX and SOD in ventricular blood of the citrus B group were found to be significantly elevated,while the contents of NO and LDH in myocardial MDA and ventricle were observed to be significantly reduced.The number of eNOS-positive cells was significantly increased,while the number of iNOS-positive cells was significantly decreased.The difference was statistically significant when compared with the AMI-RI group(P<0.05).The changes observed in the above indicators in the citrus C group were more pronounced than those observed in the citrus B group.The difference between the citrus C and the B group was statistically significant(P<0.05),indicating that this effect is concentration dependent.[Conclusions]In addition to its ability to inhibit myocardial lipid peroxidation during AMI-RI by increasing SOD activity,naringenin may also affect the synthesis and release of NO by regulating eNOS and iNOS,thereby achieving protection against AMI-RI.One effect is enhanced as the dose of the drug increases.展开更多
Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast mi...Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast microvilli (stbm) and l-arginine nitrosyl methyl ester were screened out via caudal vein injection. Twenty gestational hypertension-preeclampsia model SD (Sprague Dawley) rats successfully induced by L-NAME (L-arginine Nitrosyl methyl ester) were randomly divided into 2 groups (model group and Danshen injection group, n = 10). Then another 10 normal pregnant SD rats without model were selected as blank control group. The Salvia miltiorrhiza injection group was given Salvia miltiorrhiza injection (0.5 g?kg?1?d?1) through tail vein, and the control group and model group were given equal volume of normal saline through tail vein injection. All three groups were treated by tail vein injection once a day (d) for 7 days. After treatment, heart rate (HR), Systolic pressure (SP), diastolic pressure (DP) and mean arterial pressure (MAP) were measured by tail artery. Left ventricular end-diastolic diameter (LVDd) and Left ventricular end systolic diameter (LVDs) were recorded by echocardiography. Left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (left ventricular ejection) fraction, LVEF) and the maximum rate of increase/decrease of left ventricular pressure during isovolemic systole (+dp/dtmax/?dp/dtmax);Endothelin-1 (ET-1) levels in rat tail vein blood were detected by ELISA. Results: SP, DP, MP, HR, LVSP, LVDs and ?dp/dtmaxx were all decreased, plasma ET-1 expression was low, and LVDd, LVEDP, LVEF, and +dp/dtmax were all increased in the Salvia miltiorroot injection group, with statistical significance compared to the model group (p Conclusion: Salvia miltiorrhiza injection can improve the cardiac function and reduce blood pressure in rats with pregnancy-induced hypertension and preeclampsia, and the mechanism may be related to alleviating systemic arteriolar spasm by regulating ET-1 level.展开更多
Testosterone deficiency is common in male patients with chronic obstructive pulmonary disease (COPD) and may correlate with the deterioration of COPD. Clinical research suggests that testosterone replacement therapy m...Testosterone deficiency is common in male patients with chronic obstructive pulmonary disease (COPD) and may correlate with the deterioration of COPD. Clinical research suggests that testosterone replacement therapy may slow the COPD progression, but the specific biological pathway remains unclear. In this study, we explored the effect of testosterone on pulmonary inflammation in male COPD rats. The animals were co-treated with lipopolysaccharide (LPS) and cigarette to induce COPD. In COPD rats, nuclear respiratory factor 1 (NRF1) and NF-κB p65 were upregulated. In cigarette smoke extract (CSE)-, LPS-, or the combination of CSE and LPS-treated L132 cells, NRF1 and p65 were also upregulated. Silencing NRF1 resulted in the downregulation of p65. ChIP‒seq, ChIP‒qPCR, and luciferase results showed that NRF1 transcriptionally regulated p65. Both male and female COPD rats showed an upregulated NRF1 level and similar pulmonary morphology. But NRF1 was further upregulated in male castrated rats. Further supplementing testosterone in castrated male rats significantly reduced NRF1, pulmonary lesions, and inflammation. Supplementation of testosterone also reduced the phosphorylation of p65 and IKKβ induced by LPS or CSE in L132 cells. Our results suggest that testosterone plays a protective role in pulmonary epithelial inflammation of COPD through inhibition of NRF1-derived NF-κB signaling and the phosphorylation of p65.展开更多
High-altitude cerebral edema(HACE)is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude.The formation of HACE is affected by both vasogenic and cytotoxic ...High-altitude cerebral edema(HACE)is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude.The formation of HACE is affected by both vasogenic and cytotoxic edema.The over-activated microglia potentiate the damage of blood-brain barrier(BBB)and exacerbate cytotoxic edema.In light with the activation of microglia in HACE,we aimed to investigate whether the over-activated microglia were the key turning point of acute mountain sickness to HACE.In in vivo experiments,by exposing mice to hypobaric hypoxia(7000 m above sea level)to induce HACE model,we found that microglia were activated and migrated to blood vessels.Microglia depletion by PLX5622 obviously relieved brain edema.In in vitro experiments,we found that hypoxia induced cultured microglial activation,leading to the destruction of endothelial tight junction and astrocyte swelling.Up-regulated nuclear respiratory factor 1(NRF1)accelerated pro-inflammatory factors through transcriptional regulation on nuclearfactorkappa B p65(NF-kB p65)and mitochondrial transcription factorA(TFAM)in activated microglia under hypoxia.NRF1 also up-regulated phagocytosis by transcriptional regulation on caveolin-1(CAV-1)and adaptorrelated protein complex 2 subunit beta(AP2B1).The present study reveals a new mechanism in HACE:hypoxia over-activates microglia through up-regulation of NRF1,which both induces inflammatory response through transcriptionally activating NF-kB p65 and TFAM,and enhances phagocytic function through up-regulation of CAV-1 and AP2B1;hypoxia-activatedmicroglia destroy the integrity of BBB and release pro-inflammatory factors that eventually induce HACE.展开更多
文摘[Objectives]To investigate the protective mechanism of naringenin on acute myocardial ischemia-reperfusion injury(AMI-RI)in Sprague-Dawley(SD)rats.[Methods]A total of 32 SD rats with AMI-RI model construction were randomly divided into AMI-RI model control group and citrus pigment A/B/C groups(n=8).The naringenin A,B,and C groups were administrated 20,40 and 80 mg/(kg•d)for 10 d.The AMI group served as the negative control and was not treated.At the conclusion of the treatment regimen,a sample of intraventricular blood was collected for the purpose of measuring lactate dehydrogenase(LDH),glutathione peroxidase(GLH-PX),nitric oxide(NO),and superoxide dismutase(SOD)levels.Additionally,myocardial tissue was identified within the ischemic region.The content of malondialdehyde(MDA)was determined by inducing nitric oxide synthase(iNOS)and endodermal nitric oxide synthase(eNOS)positive cells in the left anterior descending coronary artery.[Results]Following citrus treatment,the contents of GLH-PX and SOD in ventricular blood of the citrus B group were found to be significantly elevated,while the contents of NO and LDH in myocardial MDA and ventricle were observed to be significantly reduced.The number of eNOS-positive cells was significantly increased,while the number of iNOS-positive cells was significantly decreased.The difference was statistically significant when compared with the AMI-RI group(P<0.05).The changes observed in the above indicators in the citrus C group were more pronounced than those observed in the citrus B group.The difference between the citrus C and the B group was statistically significant(P<0.05),indicating that this effect is concentration dependent.[Conclusions]In addition to its ability to inhibit myocardial lipid peroxidation during AMI-RI by increasing SOD activity,naringenin may also affect the synthesis and release of NO by regulating eNOS and iNOS,thereby achieving protection against AMI-RI.One effect is enhanced as the dose of the drug increases.
文摘Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast microvilli (stbm) and l-arginine nitrosyl methyl ester were screened out via caudal vein injection. Twenty gestational hypertension-preeclampsia model SD (Sprague Dawley) rats successfully induced by L-NAME (L-arginine Nitrosyl methyl ester) were randomly divided into 2 groups (model group and Danshen injection group, n = 10). Then another 10 normal pregnant SD rats without model were selected as blank control group. The Salvia miltiorrhiza injection group was given Salvia miltiorrhiza injection (0.5 g?kg?1?d?1) through tail vein, and the control group and model group were given equal volume of normal saline through tail vein injection. All three groups were treated by tail vein injection once a day (d) for 7 days. After treatment, heart rate (HR), Systolic pressure (SP), diastolic pressure (DP) and mean arterial pressure (MAP) were measured by tail artery. Left ventricular end-diastolic diameter (LVDd) and Left ventricular end systolic diameter (LVDs) were recorded by echocardiography. Left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (left ventricular ejection) fraction, LVEF) and the maximum rate of increase/decrease of left ventricular pressure during isovolemic systole (+dp/dtmax/?dp/dtmax);Endothelin-1 (ET-1) levels in rat tail vein blood were detected by ELISA. Results: SP, DP, MP, HR, LVSP, LVDs and ?dp/dtmaxx were all decreased, plasma ET-1 expression was low, and LVDd, LVEDP, LVEF, and +dp/dtmax were all increased in the Salvia miltiorroot injection group, with statistical significance compared to the model group (p Conclusion: Salvia miltiorrhiza injection can improve the cardiac function and reduce blood pressure in rats with pregnancy-induced hypertension and preeclampsia, and the mechanism may be related to alleviating systemic arteriolar spasm by regulating ET-1 level.
基金The study was supported by grants from the National Natural Science Foundation of China(31671206,81702874,81873924,and 81971131).
文摘Testosterone deficiency is common in male patients with chronic obstructive pulmonary disease (COPD) and may correlate with the deterioration of COPD. Clinical research suggests that testosterone replacement therapy may slow the COPD progression, but the specific biological pathway remains unclear. In this study, we explored the effect of testosterone on pulmonary inflammation in male COPD rats. The animals were co-treated with lipopolysaccharide (LPS) and cigarette to induce COPD. In COPD rats, nuclear respiratory factor 1 (NRF1) and NF-κB p65 were upregulated. In cigarette smoke extract (CSE)-, LPS-, or the combination of CSE and LPS-treated L132 cells, NRF1 and p65 were also upregulated. Silencing NRF1 resulted in the downregulation of p65. ChIP‒seq, ChIP‒qPCR, and luciferase results showed that NRF1 transcriptionally regulated p65. Both male and female COPD rats showed an upregulated NRF1 level and similar pulmonary morphology. But NRF1 was further upregulated in male castrated rats. Further supplementing testosterone in castrated male rats significantly reduced NRF1, pulmonary lesions, and inflammation. Supplementation of testosterone also reduced the phosphorylation of p65 and IKKβ induced by LPS or CSE in L132 cells. Our results suggest that testosterone plays a protective role in pulmonary epithelial inflammation of COPD through inhibition of NRF1-derived NF-κB signaling and the phosphorylation of p65.
基金The study was supported by grants from the National Natural Science Foundation of China(31671206 and 81873924)Key Laboratory of Extreme Environmental Medicine,the Ministry of Education(KL2019GY011).
文摘High-altitude cerebral edema(HACE)is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude.The formation of HACE is affected by both vasogenic and cytotoxic edema.The over-activated microglia potentiate the damage of blood-brain barrier(BBB)and exacerbate cytotoxic edema.In light with the activation of microglia in HACE,we aimed to investigate whether the over-activated microglia were the key turning point of acute mountain sickness to HACE.In in vivo experiments,by exposing mice to hypobaric hypoxia(7000 m above sea level)to induce HACE model,we found that microglia were activated and migrated to blood vessels.Microglia depletion by PLX5622 obviously relieved brain edema.In in vitro experiments,we found that hypoxia induced cultured microglial activation,leading to the destruction of endothelial tight junction and astrocyte swelling.Up-regulated nuclear respiratory factor 1(NRF1)accelerated pro-inflammatory factors through transcriptional regulation on nuclearfactorkappa B p65(NF-kB p65)and mitochondrial transcription factorA(TFAM)in activated microglia under hypoxia.NRF1 also up-regulated phagocytosis by transcriptional regulation on caveolin-1(CAV-1)and adaptorrelated protein complex 2 subunit beta(AP2B1).The present study reveals a new mechanism in HACE:hypoxia over-activates microglia through up-regulation of NRF1,which both induces inflammatory response through transcriptionally activating NF-kB p65 and TFAM,and enhances phagocytic function through up-regulation of CAV-1 and AP2B1;hypoxia-activatedmicroglia destroy the integrity of BBB and release pro-inflammatory factors that eventually induce HACE.
