Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally int...Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally into rats for one month to induce cardiac hypertrophy.L-carvone(25 and 100 mg/kg)was administered orally to treat cardiac hypertrophy.The cardioprotective activity of L-carvone was evaluated by electrocardiogram,histopathological analysis as well as determination of biochemical parameters and enzymatic markers.Results:L-carvone from Mentha spicata L.at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy,as evidenced by reduced QRS interval on electrocardiogram,and decreased heart weight and heart index.In addition,both doses of L-carvone markedly lowered the levels of glucose,total protein,low-density lipoprotein cholesterol,aspartate transaminase,alanine transaminase,lactate dehydrogenase,creatine kinase MB,troponin-Ⅰ,N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level(P<0.05).Moreover,L-carvone alleviated contraction band necrosis,and reorganized the myofibrils with normal striations and myocytes as well as normal nuclei in cardiac histoarchitecture of rats with isoproterenol-induced cardiac hypertrophy.Conclusions:L-carvone from Mentha spicata L.leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.展开更多
Objective:To investigate the cardioprotective effect of naringenin against isoproterenol(ISO)-induced cardiotoxicity in rats.Methods:Rats were divided into five groups:the normal group,the ISO group(85 mg/kg b.w.);the...Objective:To investigate the cardioprotective effect of naringenin against isoproterenol(ISO)-induced cardiotoxicity in rats.Methods:Rats were divided into five groups:the normal group,the ISO group(85 mg/kg b.w.);the ISO+naringenin(50 mg/kg b.w.)group,the ISO+naringenin(100 mg/kg b.w.)group and the ISO+propranolol(10 mg/kg b.w.)group.Plasma creatine kinase-MB(CK-MB),cardiac troponin T,lactate dehydrogenase,brain natriuretic peptide(BNP),and IL-10,as well as cardiac transforming growth factor-β1(TGF-β1),vascular endothelial growth factor(VEGF)and malondialdehyde(MDA)were examined.In addition,NLRP3 and mRNA-208a expressions were evaluated by RT-PCR analysis.Histopathological examination was also performed to assess cardiac damages.Results:Naringenin treatment significantly decreased plasma lactate dehydrogenase,CK-MB,cardiac troponin T,BNP,and IL-10,as well as cardiac TGF-β1,VEGF,and MDA while increasing p-Akt and superoxide dismutase in ISO-administered rats.It also reduced NLRP3 and mRNA-208a gene expression levels.Furthermore,naringenin improved ISO-induced cardiac damage.Conclusions:Naringenin attenuates myocardial dysfunction in ISO-treated rats by decreasing oxidative stress and increasing cardiac endogenous antioxidant system,which may be modulated partly by improvement of NLRP3 and mRNA-208a gene expression.展开更多
Objective:To investigate the cardioprotective effect of beta-glucan against isoproterenol-induced cardiotoxicity in rats,and elucidate the underlying mechanism.Methods:Rats were orally pretreated with beta-glucan(40 m...Objective:To investigate the cardioprotective effect of beta-glucan against isoproterenol-induced cardiotoxicity in rats,and elucidate the underlying mechanism.Methods:Rats were orally pretreated with beta-glucan(40 mg/kg body weight)for 30 d,and isoproterenol(20 mg/100 g body weight)was administered on days 31 and 32.The effects of beta-glucan on markers of cardiac injury,hemodynamic changes,production of proinflammatory cytokines,and the corresponding mRNA expressions were evaluated.In addition,histological analysis was performed.Results:Pretreatment with beta-glucan prevented isoproterenol-induced cardiac injury by preserving the structural and functional integrity of the plasma membrane and attenuating the production of proinflammatory cytokines(NF-κB,TNF-α,IL-6,IL-1β,and IFN-γ)in the heart.Moreover,beta-glucan significantly downregulated the mRNA expression of ACE,AT1R,TNF-α,IL-6,NF-κB,caspase-3,TLR-4,and Bax,and upregulated Bcl-2 in the heart.At the same time,pretreatment with beta-glucan alleviated myocardial damage as reflected in a reduction in myonecrosis,edema,and erythrocyte extravasation with almost imperceptible inflammation.Conclusions:Beta-glucan can protect against isoproterenol-induced cardiotoxicity by attenuating cardiac inflammation and apoptosis and regulating the ACE-AT1R axis,thereby preventing cardiac remodeling.展开更多
The present study investigated the effect of an herbal extract-supplemented cardiomyopeptin preparation (HECP), in the rat model of chronic heart failure. HECP pre-/co-treatment at a daily dose of 0.072 to 0.124 g/kg ...The present study investigated the effect of an herbal extract-supplemented cardiomyopeptin preparation (HECP), in the rat model of chronic heart failure. HECP pre-/co-treatment at a daily dose of 0.072 to 0.124 g/kg for 30 days protected against isoproterenol (ISO)-induced chronic myocardial damage in rats in a dose-dependent manner, with the extent of protection, as assessed by plasma cardiac troponin I level, being up to 76%. The cardioprotection afforded by HECP was associated with the enhancement of myocardial mitochondrial antioxidant status, amelioration of plasma parameters on cardiac dysfunction and hypertrophy, as well as an increase in myocardial endothelial nitric oxide synthase activity. Myocardial apoptotic and anti-apoptotic parameters were suppressed and stimulated, respectively. The cardioprotection afforded by HECP was accompanied by an increase in exercise capacity, an indirect functional index of the myocardium, in ISO-challenged rats. In conclusion, HECP may offer a promising prospect in preventing chronic heart failure in human subjects.展开更多
Objective:To assess the protective effects of lycopene on electrocardiographic,hemodynamic, biochemical and apoptotic changes in isoproterenol induced myocardial infarction.Methods: Myocardial infarction was induced i...Objective:To assess the protective effects of lycopene on electrocardiographic,hemodynamic, biochemical and apoptotic changes in isoproterenol induced myocardial infarction.Methods: Myocardial infarction was induced in rats by subcutaneous injection of isoproterenol(200 mg/kg) for two consecutive days at an interval of 24 h.Rats were treated with lycopene(10 mg/kg/day, p.o.) for a period of 30 days and isoproterenol(ISO) was injected on the 29th and 30th day.At the end of experiment i.e.on the 31st day electrocardiographic,hemodynamic,biochemical and apoptotic changes were monitored from control and experimental groups.Results:ISO injected ruts showed a significant alteration in electrocardiograph pattern and hemodynamic changes(i.e. systolic,diastolic and mean arterial pressure).It also showed significant increase in C-reactive protein,myeloperoxidase,nitrite levels and Caspase-3 protease activity.In addition,it also exhibited alteration in the levels of electrolytes(Na^+,K^+ and Ca^(2+),vitamin E,uric acid and serum protein.Cel electrophoresis of ISO injected rats showed increase in DNA fragmentation.Triphenyl tetrazolium chloride staining of the heart section shows increase area of infarction in ISO injected rats.Pre-co-treatment with lycopene significantly prevented the ISO induced ullerution in ECC, haemodynamic,biochemical and apoptotic changes.Conclusions:The present result shows that treatment of lycopene in ISO injected rats significantly attenuates induced myocardial infarction.展开更多
Objective: To evaluate the cardioprotective effect of Nigella sativa L.(N.sativa) in isoproterenol-induced myocardial infarction(MI).Methods: Groups were treated with different doses of ethanol extract of N.sativa(EEN...Objective: To evaluate the cardioprotective effect of Nigella sativa L.(N.sativa) in isoproterenol-induced myocardial infarction(MI).Methods: Groups were treated with different doses of ethanol extract of N.sativa(EENS)and N.sativa oil alone and along with enalapril for 28 days.MI was induced by subcutaneous administration of isoproterenol(85 mg/kg) in two consecutive doses.Levels of cardiac biomarkers and antioxidant enzymes such as creatine kinase–N-acetyl-L-cysteine, lactate dehydrogenase, aspartate aminotransferase, malondialdehyde, superoxide dismutase, reduced glutathione and catalase were evaluated along with gross histopathological examination.Results: Isoproterenol(85 mg/kg) induced MI by causing the significant(P < 0.01)reduction in the activity of cardiac biomarkers(creatine kinase–N-acetyl-L-cysteine,lactate dehydrogenase, aspartate aminotransferase) and antioxidant markers(superoxide dismutase, catalase, glutathione) along with significant(P < 0.01) increase in the level of malondialdehyde.Furthermore, histopathological evaluation also confirmed the isoproterenol-induced MI.Pretreatment with EENS(800 mg/kg) and combination of EENS(800 mg/kg) with enalapril(1 mg/kg) significantly(P < 0.01) prevented the development of these alteration and restored activity of cardiac biomarkers as well as antioxidant markers almost near to normal levels.Histopathological evaluation of cardiac tissue further confirmed the restoration of biochemical activity.Conclusions: Experimental findings thus indicate that EENS(800 mg/kg) demonstrated cardioprotective effect against isoproterenol-induced MI by restoring cardiac biomarkers and antioxidant status.展开更多
One unknown impurity(Imp-Ⅱ) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. ...One unknown impurity(Imp-Ⅱ) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2-ylamino)ethyl]benzene-1,2-diol(Imp-Ⅱ) using the liquid chromatography–mass spectrophotometry(LC–MS) analysis. Imp-Ⅱ was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as ~1H,^(13)C, DEPT(1D NMR), HSQC(2D NMR)and infrared spectroscopy(IR), and retention time and purity with HPLC followed by the chemical synthesis.Due to less removable nature of Imp-Ⅱ during the purification, the synthetic process was optimized proficiently to control the formation of Imp-Ⅱ below to the limit < 0.12% in the course of reaction. The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard.The most probable mechanism for the formation of Imp-Ⅱ was discussed in details.展开更多
OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropr...OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.展开更多
OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropr...OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.展开更多
The application of the laser Raman spectroscopic(LRS) technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol(ISO) was described.Animal model of myocardial ischemia was ...The application of the laser Raman spectroscopic(LRS) technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol(ISO) was described.Animal model of myocardial ischemia was established for rats induced by ISO.Rats were randomly divided into four groups as normal group and myocardial ischemia groups.We observed the successful myocardial ischemia model via serum enzymes levels and hematoxylin-eosin(HE) staining,and detected the liver tissue of the rats from normal group and liver tissue of the rats from myocardial ischemia groups via UV-Vis spectroscopy(UV-Vis) and LRS,and the changes of the absorbance spectra were compared in the above four different groups.The results show that ISO can induce rat myocardial ischemia successfully.The spectrum of normal liver tissue supernatant exhibits a strong absorption band at 968 nm,but no absorption band appears in the spectra of liver tissue supernatant solutions from the rats with myocardial ischemia induction after 2,12 and 72 h presented at 968 nm.LRS results show that Raman intensities of the precipitates suffered from ISO-treatment after 2,12 and 72 h were obviously increased compared with that of the precipitate of the liver tissue of the normal rats suffered from 0.9 g/L normal saline(NS) treatment.These results indicate that LRS and UV-Vis can be harmless,nondestructive,rapid and effective methods for analyzing different pathological specimens of liver tissue from myocardial ischemia rats.展开更多
Abstract Objective:To explore whether successful valvuloplasty increases mitral valve reserve capacity in patients with mitral stenosis.Methods:Thirty-eight patients with pure rheumatic mitral stenosis underwent isopr...Abstract Objective:To explore whether successful valvuloplasty increases mitral valve reserve capacity in patients with mitral stenosis.Methods:Thirty-eight patients with pure rheumatic mitral stenosis underwent isoproterenol stress echocardiography before and after successful percutaneous balloon valvuloplasty.The mi-tral valve area(by direct planimetry of two-dimensional echocardiography),mean transmitral pressure gradi-ent (by continuous-wave Doppler echocardiography),and cardiac output(by M-mode echocardiography) were measured at rest and under isoproterenol infusion to achieve heart rate of different stages.Results:Be-tween the measurements before and after valvuloplasty, significant differences were observed in the mitral valve area(0.91±0.28 vs 1.87±0.23cm^2,P<0.01),mean transmitral pressure gradient(12.5±6.3 vs 3.9±1.9mmHg,P<0.01)and cardiac output(3.93±1.44 vs 4.73±1.01L/min,P<0.05) at rest.Be-fore valvuloplasty,the mean transmitral pressure gradient increased significantly(P<0.01) as heart rate in-creased,but there were no significant differences in the measurements of mitral valve area and cardiac output (both P>0.05).In contrast,there was a significant increase after valvuloplasty in the mean transmitral pressure gradient(P<0.01),but both mitral valve area and cardiac output further increased (both P<0.01) as heart rate increased.Moreover,valvuloplasty decreased the mean transmitral pressure gradient at peak heart rate from 23.0±4.5 to 7.75±2.30mmHg(P<0.01)under submaximal stress.Conclusion:Successful percutanneous balloon valvuloplasty soon causes a significant increase of mitral valve reserve capaci-ty in patients with mitral stenosis,which is conspicuously manifested under condition of hemodynamic stress.Stress echocardiography provides a safe ,feasible and non-invasive means of assessing the reserve capacity.展开更多
Objective:Dalbergia odorifera has long been used as a Chinese herbal medicine for the treatment of cardiovascular and cerebrovascular diseases.This study aimed to determine the potential myocardial protective effect a...Objective:Dalbergia odorifera has long been used as a Chinese herbal medicine for the treatment of cardiovascular and cerebrovascular diseases.This study aimed to determine the potential myocardial protective effect and possible mechanism of action of D.odor ife ra essential oil(DOEO).Materials and Methods:The essential oil of D.odorifera was extracted by hydrodistillation.The cardioprotective effects of DOEO were examined by histopathological observation,myocardial enzyme detection,peroxidation,anti-oxidant level detection,and related protein expression.The compounds in the blood were identified by gas chromatography-mass spectrometry.Results:These results showed that DOEO had significant myocardial cell protection,with IC50 values ranging from 17.64 to 24.78μg/mL in vitro.Compared to the myocardial ischemia group,the DOEO pretreatment groups had lower levels of myocardial injury,creatinine kinase,lactate dehydrogenase,alanine transaminase,aspartate transaminase,hydrogen peroxide,and nitric oxide,and higher levels of glutathione and superoxide dismutase.In addition,DOEO pretreatment significantly increased Na+-K+-ATPase and Ca2+-ATPase levels.Moreove r,immunohistochemical e xperiments showed that DOEO remarkably increased the protein levels of NF-E2-related nuclear factor 2(Nrf2)and heme oxygenase-1(HO-1)and reduced the expression of apoptotic caspases,including caspase 3 and caspase 9.The main components of the blood were transnerolidol and nerolidol oxide.Overall,the study showed that DOEO displayed myocardial protection by upregulating the NF-E2-related nuclear factor-antioxidant response element(Nrf2-ARE)and caspase pathways.DOEO has a therapeutic effect on MI by inhibiting the oxidant and apoptotic effects.Conclusions:D.odorifera may be a potential candidate drug for treating myocardial ischemic injury.展开更多
OBJECTIVE: To investigate the effect of acupuncture at Neiguan(PC 6) on cardiac function using echocardiography in rat models of myocardial ischemia(MI) induced by isoproterenol(ISO).METHODS: Twenty-seven Sprague-Dawl...OBJECTIVE: To investigate the effect of acupuncture at Neiguan(PC 6) on cardiac function using echocardiography in rat models of myocardial ischemia(MI) induced by isoproterenol(ISO).METHODS: Twenty-seven Sprague-Dawley rats were randomly assigned to normal, model, and acupuncture groups. The model and acupuncture groups were given injections of ISO(85 mg/kg) to establish the MI model. After model establishment,the acupuncture group was treated with acupuncture at Neiguan(PC 6) for 30 min. Echocardiography was used to monitor diastolic and systolic function for 30 min starting from the time after the acupuncture needles were removed. Changes in the length of left ventricular internal diameter at end-diastole(LVIDd), length of left ventricular internal diameter at end-systole(LVIDs), the ratio of mitral peak velocity at early diastole and atrial contraction(E/A), ejection fraction(EF), fractional shortening(FS), and stroke volume(SV) were measured.RESULTS: Compared with the model group at 0and 15 min after needles were removed, the means of LVIDd and LVIDs were significantly lower(P <0.01) and E/A, EF, FS, and SV significantly higher(P < 0.01) in the acupuncture group. In the acupuncture group, the means of LVIDd and LVIDs15 min after the needles were removed were significantly higher(P < 0.01) than those at 0 min. The means of E/A, EF, FS, and SV significantly decreased(P < 0.01) from 0 to 15 min in the acupuncture group.CONCLUSION: These findings indicate that acupuncture at Neiguan(PC 6) can affect cardiac function by increasing left ventricular diastolic and systolic function in MI rat models, but the effect only lasts for 15 min.展开更多
Objective:To evaluate the effects of Huoxin Pill(活心丸,HXP)on cardiac fibrosis and heart failure(HF)in isoproterenol(ISO)-induced HF rats.Methods:Thirty Wistar rats were randomly divided into 5 groups including contr...Objective:To evaluate the effects of Huoxin Pill(活心丸,HXP)on cardiac fibrosis and heart failure(HF)in isoproterenol(ISO)-induced HF rats.Methods:Thirty Wistar rats were randomly divided into 5 groups including control,HF,isosorbide mononitrate(ISMN),HXP low(HXP-L),and HXP high(HXP-H)groups(n=6 for each group)according to the complete randomization method.Rats were pretreated with ISMN(5 mg/kg daily),low concentration of HXP(10 mg/kg daily)or high concentration of HXP(30 mg/kg daily)or equal volume of saline by intragastric administration for 1 week,followed by intraperitoneal injection of ISO(10 mg/kg,14 days),and continually intragastric administrated with above medicines or saline for additional 6 weeks.The effects of HXP treatment on the cardiac function,heart weight index(HWI),pathological changes,and collagen content were further assessed.Moreover,the role of HXP on activation of transforming growth factor-β1(TGF-β1)/Smads pathway was further explored using immunohistochemistry(IHC)and Westernblot assay.Results:HXP treatment significantly alleviated the decrease of ejection fraction(EF)and fractional shortening(FS),while decreased the elevation of left ventricular end-systolic volume(LVESV)in ISO-induced HF rats(P<0.05).Moreover,HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB(CK-MB,P<0.05),as well as pathological changes in ISO-induced HF rats.Further determination indicated that HXP treatment alleviated the elevation of collagenⅠand collagenⅢprotein expression in cardiac tissues of ISO-induced HF rats.Furthermore,HXP treatment significantly down-regulated the increase of TGF-β1 and p-Smad2/3 protein expression in cardiac tissues of HF rats(P<0.05),while did not affect the expression of total Smad2/3.Conclusions:HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-β1/Smad2/3 pathway.展开更多
A sensitive electrochemical sensor for the determination of cysteamine(CA) was developed using a modified multiwall carbon nanotube paste electrode(MWCNTPE) with isoproterenol(ISPT) as a mediator.This modified electro...A sensitive electrochemical sensor for the determination of cysteamine(CA) was developed using a modified multiwall carbon nanotube paste electrode(MWCNTPE) with isoproterenol(ISPT) as a mediator.This modified electrode showed very high electrocatalytic activity for the anodic oxidation of CA.Under the optimized conditions,the electrocatalytic peak current showed a linear relationship with CA concentration in the range of 0.3–450.0 mmol/L with a detection limit of 0.09 mmol/L CA.The modified electrode was used for the determination of CA in real samples such as urine and drug samples.展开更多
文摘Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally into rats for one month to induce cardiac hypertrophy.L-carvone(25 and 100 mg/kg)was administered orally to treat cardiac hypertrophy.The cardioprotective activity of L-carvone was evaluated by electrocardiogram,histopathological analysis as well as determination of biochemical parameters and enzymatic markers.Results:L-carvone from Mentha spicata L.at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy,as evidenced by reduced QRS interval on electrocardiogram,and decreased heart weight and heart index.In addition,both doses of L-carvone markedly lowered the levels of glucose,total protein,low-density lipoprotein cholesterol,aspartate transaminase,alanine transaminase,lactate dehydrogenase,creatine kinase MB,troponin-Ⅰ,N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level(P<0.05).Moreover,L-carvone alleviated contraction band necrosis,and reorganized the myofibrils with normal striations and myocytes as well as normal nuclei in cardiac histoarchitecture of rats with isoproterenol-induced cardiac hypertrophy.Conclusions:L-carvone from Mentha spicata L.leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.
文摘Objective:To investigate the cardioprotective effect of naringenin against isoproterenol(ISO)-induced cardiotoxicity in rats.Methods:Rats were divided into five groups:the normal group,the ISO group(85 mg/kg b.w.);the ISO+naringenin(50 mg/kg b.w.)group,the ISO+naringenin(100 mg/kg b.w.)group and the ISO+propranolol(10 mg/kg b.w.)group.Plasma creatine kinase-MB(CK-MB),cardiac troponin T,lactate dehydrogenase,brain natriuretic peptide(BNP),and IL-10,as well as cardiac transforming growth factor-β1(TGF-β1),vascular endothelial growth factor(VEGF)and malondialdehyde(MDA)were examined.In addition,NLRP3 and mRNA-208a expressions were evaluated by RT-PCR analysis.Histopathological examination was also performed to assess cardiac damages.Results:Naringenin treatment significantly decreased plasma lactate dehydrogenase,CK-MB,cardiac troponin T,BNP,and IL-10,as well as cardiac TGF-β1,VEGF,and MDA while increasing p-Akt and superoxide dismutase in ISO-administered rats.It also reduced NLRP3 and mRNA-208a gene expression levels.Furthermore,naringenin improved ISO-induced cardiac damage.Conclusions:Naringenin attenuates myocardial dysfunction in ISO-treated rats by decreasing oxidative stress and increasing cardiac endogenous antioxidant system,which may be modulated partly by improvement of NLRP3 and mRNA-208a gene expression.
文摘Objective:To investigate the cardioprotective effect of beta-glucan against isoproterenol-induced cardiotoxicity in rats,and elucidate the underlying mechanism.Methods:Rats were orally pretreated with beta-glucan(40 mg/kg body weight)for 30 d,and isoproterenol(20 mg/100 g body weight)was administered on days 31 and 32.The effects of beta-glucan on markers of cardiac injury,hemodynamic changes,production of proinflammatory cytokines,and the corresponding mRNA expressions were evaluated.In addition,histological analysis was performed.Results:Pretreatment with beta-glucan prevented isoproterenol-induced cardiac injury by preserving the structural and functional integrity of the plasma membrane and attenuating the production of proinflammatory cytokines(NF-κB,TNF-α,IL-6,IL-1β,and IFN-γ)in the heart.Moreover,beta-glucan significantly downregulated the mRNA expression of ACE,AT1R,TNF-α,IL-6,NF-κB,caspase-3,TLR-4,and Bax,and upregulated Bcl-2 in the heart.At the same time,pretreatment with beta-glucan alleviated myocardial damage as reflected in a reduction in myonecrosis,edema,and erythrocyte extravasation with almost imperceptible inflammation.Conclusions:Beta-glucan can protect against isoproterenol-induced cardiotoxicity by attenuating cardiac inflammation and apoptosis and regulating the ACE-AT1R axis,thereby preventing cardiac remodeling.
文摘The present study investigated the effect of an herbal extract-supplemented cardiomyopeptin preparation (HECP), in the rat model of chronic heart failure. HECP pre-/co-treatment at a daily dose of 0.072 to 0.124 g/kg for 30 days protected against isoproterenol (ISO)-induced chronic myocardial damage in rats in a dose-dependent manner, with the extent of protection, as assessed by plasma cardiac troponin I level, being up to 76%. The cardioprotection afforded by HECP was associated with the enhancement of myocardial mitochondrial antioxidant status, amelioration of plasma parameters on cardiac dysfunction and hypertrophy, as well as an increase in myocardial endothelial nitric oxide synthase activity. Myocardial apoptotic and anti-apoptotic parameters were suppressed and stimulated, respectively. The cardioprotection afforded by HECP was accompanied by an increase in exercise capacity, an indirect functional index of the myocardium, in ISO-challenged rats. In conclusion, HECP may offer a promising prospect in preventing chronic heart failure in human subjects.
基金Supported by All India Couneil for Technical Education(AICTE)(Grant No.1-10/RID/NDF-PG/(28)/2007-08)
文摘Objective:To assess the protective effects of lycopene on electrocardiographic,hemodynamic, biochemical and apoptotic changes in isoproterenol induced myocardial infarction.Methods: Myocardial infarction was induced in rats by subcutaneous injection of isoproterenol(200 mg/kg) for two consecutive days at an interval of 24 h.Rats were treated with lycopene(10 mg/kg/day, p.o.) for a period of 30 days and isoproterenol(ISO) was injected on the 29th and 30th day.At the end of experiment i.e.on the 31st day electrocardiographic,hemodynamic,biochemical and apoptotic changes were monitored from control and experimental groups.Results:ISO injected ruts showed a significant alteration in electrocardiograph pattern and hemodynamic changes(i.e. systolic,diastolic and mean arterial pressure).It also showed significant increase in C-reactive protein,myeloperoxidase,nitrite levels and Caspase-3 protease activity.In addition,it also exhibited alteration in the levels of electrolytes(Na^+,K^+ and Ca^(2+),vitamin E,uric acid and serum protein.Cel electrophoresis of ISO injected rats showed increase in DNA fragmentation.Triphenyl tetrazolium chloride staining of the heart section shows increase area of infarction in ISO injected rats.Pre-co-treatment with lycopene significantly prevented the ISO induced ullerution in ECC, haemodynamic,biochemical and apoptotic changes.Conclusions:The present result shows that treatment of lycopene in ISO injected rats significantly attenuates induced myocardial infarction.
基金the University Grants Commission,New Delhi (Grant No.7-268/2009 BSR) for fellowship
文摘Objective: To evaluate the cardioprotective effect of Nigella sativa L.(N.sativa) in isoproterenol-induced myocardial infarction(MI).Methods: Groups were treated with different doses of ethanol extract of N.sativa(EENS)and N.sativa oil alone and along with enalapril for 28 days.MI was induced by subcutaneous administration of isoproterenol(85 mg/kg) in two consecutive doses.Levels of cardiac biomarkers and antioxidant enzymes such as creatine kinase–N-acetyl-L-cysteine, lactate dehydrogenase, aspartate aminotransferase, malondialdehyde, superoxide dismutase, reduced glutathione and catalase were evaluated along with gross histopathological examination.Results: Isoproterenol(85 mg/kg) induced MI by causing the significant(P < 0.01)reduction in the activity of cardiac biomarkers(creatine kinase–N-acetyl-L-cysteine,lactate dehydrogenase, aspartate aminotransferase) and antioxidant markers(superoxide dismutase, catalase, glutathione) along with significant(P < 0.01) increase in the level of malondialdehyde.Furthermore, histopathological evaluation also confirmed the isoproterenol-induced MI.Pretreatment with EENS(800 mg/kg) and combination of EENS(800 mg/kg) with enalapril(1 mg/kg) significantly(P < 0.01) prevented the development of these alteration and restored activity of cardiac biomarkers as well as antioxidant markers almost near to normal levels.Histopathological evaluation of cardiac tissue further confirmed the restoration of biochemical activity.Conclusions: Experimental findings thus indicate that EENS(800 mg/kg) demonstrated cardioprotective effect against isoproterenol-induced MI by restoring cardiac biomarkers and antioxidant status.
文摘One unknown impurity(Imp-Ⅱ) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2-ylamino)ethyl]benzene-1,2-diol(Imp-Ⅱ) using the liquid chromatography–mass spectrophotometry(LC–MS) analysis. Imp-Ⅱ was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as ~1H,^(13)C, DEPT(1D NMR), HSQC(2D NMR)and infrared spectroscopy(IR), and retention time and purity with HPLC followed by the chemical synthesis.Due to less removable nature of Imp-Ⅱ during the purification, the synthetic process was optimized proficiently to control the formation of Imp-Ⅱ below to the limit < 0.12% in the course of reaction. The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard.The most probable mechanism for the formation of Imp-Ⅱ was discussed in details.
基金The project supported by the national scientific&technological major special project″significant creation of new drugs″(2013ZX09103001-008,2012ZX09103101-078,2013ZX09508104)
文摘OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.
基金The project supported by National Natural Science Foundation of China(81573645,81603101,81473383)
文摘OBJECTIVE To investigate the protective effect of salvianolic acid A(Sal A)on isoproterenol-induced myocardial infarction in mice and its possible mechanisms.METHODS The mice were subcutaneously injected with isopropranol(ISO 8 mg·kg-1)to induce myocardial infarction and evaluated the myocardial protective effect of Sal A from mortality rate,electrocardiogram(ECG),heart function,myocardial infarction index,serum myocardial enzymes and explored its possible mechanisms from inflammatory,antioxidant and cells apoptosis.RESULTS Sal A can dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardial protection effects.ELISA results showed that Sal A can reduce the expression of myocardial inflammatory cytokines such as IL-6,TNF-α.Western blotting confirmed that Sal A can increase the expression of anti-apoptotic proteins Bcl-2,reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.CONCLUSION Sal A have displayed significant protective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to increasing of PI3K/Akt signal pathway and inhibition of cell apoptosis and inflammatory reaction.
基金Supported by the Scientific and Technological Developing Scheme of Jilin Province,China(No.201101067)
文摘The application of the laser Raman spectroscopic(LRS) technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol(ISO) was described.Animal model of myocardial ischemia was established for rats induced by ISO.Rats were randomly divided into four groups as normal group and myocardial ischemia groups.We observed the successful myocardial ischemia model via serum enzymes levels and hematoxylin-eosin(HE) staining,and detected the liver tissue of the rats from normal group and liver tissue of the rats from myocardial ischemia groups via UV-Vis spectroscopy(UV-Vis) and LRS,and the changes of the absorbance spectra were compared in the above four different groups.The results show that ISO can induce rat myocardial ischemia successfully.The spectrum of normal liver tissue supernatant exhibits a strong absorption band at 968 nm,but no absorption band appears in the spectra of liver tissue supernatant solutions from the rats with myocardial ischemia induction after 2,12 and 72 h presented at 968 nm.LRS results show that Raman intensities of the precipitates suffered from ISO-treatment after 2,12 and 72 h were obviously increased compared with that of the precipitate of the liver tissue of the normal rats suffered from 0.9 g/L normal saline(NS) treatment.These results indicate that LRS and UV-Vis can be harmless,nondestructive,rapid and effective methods for analyzing different pathological specimens of liver tissue from myocardial ischemia rats.
文摘Abstract Objective:To explore whether successful valvuloplasty increases mitral valve reserve capacity in patients with mitral stenosis.Methods:Thirty-eight patients with pure rheumatic mitral stenosis underwent isoproterenol stress echocardiography before and after successful percutaneous balloon valvuloplasty.The mi-tral valve area(by direct planimetry of two-dimensional echocardiography),mean transmitral pressure gradi-ent (by continuous-wave Doppler echocardiography),and cardiac output(by M-mode echocardiography) were measured at rest and under isoproterenol infusion to achieve heart rate of different stages.Results:Be-tween the measurements before and after valvuloplasty, significant differences were observed in the mitral valve area(0.91±0.28 vs 1.87±0.23cm^2,P<0.01),mean transmitral pressure gradient(12.5±6.3 vs 3.9±1.9mmHg,P<0.01)and cardiac output(3.93±1.44 vs 4.73±1.01L/min,P<0.05) at rest.Be-fore valvuloplasty,the mean transmitral pressure gradient increased significantly(P<0.01) as heart rate in-creased,but there were no significant differences in the measurements of mitral valve area and cardiac output (both P>0.05).In contrast,there was a significant increase after valvuloplasty in the mean transmitral pressure gradient(P<0.01),but both mitral valve area and cardiac output further increased (both P<0.01) as heart rate increased.Moreover,valvuloplasty decreased the mean transmitral pressure gradient at peak heart rate from 23.0±4.5 to 7.75±2.30mmHg(P<0.01)under submaximal stress.Conclusion:Successful percutanneous balloon valvuloplasty soon causes a significant increase of mitral valve reserve capaci-ty in patients with mitral stenosis,which is conspicuously manifested under condition of hemodynamic stress.Stress echocardiography provides a safe ,feasible and non-invasive means of assessing the reserve capacity.
基金supported by the Hainan Province Science and Technology Special Fund(ZDYF2023SHFZ141,ZDYF2018123,ZDYF2021SHFZ077)the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-032)Natural Science Foundation of Hainan Province,China(2019RC344)。
文摘Objective:Dalbergia odorifera has long been used as a Chinese herbal medicine for the treatment of cardiovascular and cerebrovascular diseases.This study aimed to determine the potential myocardial protective effect and possible mechanism of action of D.odor ife ra essential oil(DOEO).Materials and Methods:The essential oil of D.odorifera was extracted by hydrodistillation.The cardioprotective effects of DOEO were examined by histopathological observation,myocardial enzyme detection,peroxidation,anti-oxidant level detection,and related protein expression.The compounds in the blood were identified by gas chromatography-mass spectrometry.Results:These results showed that DOEO had significant myocardial cell protection,with IC50 values ranging from 17.64 to 24.78μg/mL in vitro.Compared to the myocardial ischemia group,the DOEO pretreatment groups had lower levels of myocardial injury,creatinine kinase,lactate dehydrogenase,alanine transaminase,aspartate transaminase,hydrogen peroxide,and nitric oxide,and higher levels of glutathione and superoxide dismutase.In addition,DOEO pretreatment significantly increased Na+-K+-ATPase and Ca2+-ATPase levels.Moreove r,immunohistochemical e xperiments showed that DOEO remarkably increased the protein levels of NF-E2-related nuclear factor 2(Nrf2)and heme oxygenase-1(HO-1)and reduced the expression of apoptotic caspases,including caspase 3 and caspase 9.The main components of the blood were transnerolidol and nerolidol oxide.Overall,the study showed that DOEO displayed myocardial protection by upregulating the NF-E2-related nuclear factor-antioxidant response element(Nrf2-ARE)and caspase pathways.DOEO has a therapeutic effect on MI by inhibiting the oxidant and apoptotic effects.Conclusions:D.odorifera may be a potential candidate drug for treating myocardial ischemic injury.
基金Supported by the Special Program of Chinese Medicine of the National Basic Research Program of China(973 Program):Study on the Response Characteristics of Cardiac Ion Channel to Acupuncture in Pathologic Conditions by Selecting Acupoint Along Channel(No.2012CB518503)Natural Science Fund of Liaoning Province:Study on the Effect of Acupuncture on the Neuroendocrine System and Calcium Channel Protein of Cardiomyocytes(No.2013020179)Shenyang Science and Technology Program:Study on the Influence on HDL Subclasses and RCT Pathway in apoE Knock Out Mice of Huayuqutan Reciple(No.F12-277-1-49)
文摘OBJECTIVE: To investigate the effect of acupuncture at Neiguan(PC 6) on cardiac function using echocardiography in rat models of myocardial ischemia(MI) induced by isoproterenol(ISO).METHODS: Twenty-seven Sprague-Dawley rats were randomly assigned to normal, model, and acupuncture groups. The model and acupuncture groups were given injections of ISO(85 mg/kg) to establish the MI model. After model establishment,the acupuncture group was treated with acupuncture at Neiguan(PC 6) for 30 min. Echocardiography was used to monitor diastolic and systolic function for 30 min starting from the time after the acupuncture needles were removed. Changes in the length of left ventricular internal diameter at end-diastole(LVIDd), length of left ventricular internal diameter at end-systole(LVIDs), the ratio of mitral peak velocity at early diastole and atrial contraction(E/A), ejection fraction(EF), fractional shortening(FS), and stroke volume(SV) were measured.RESULTS: Compared with the model group at 0and 15 min after needles were removed, the means of LVIDd and LVIDs were significantly lower(P <0.01) and E/A, EF, FS, and SV significantly higher(P < 0.01) in the acupuncture group. In the acupuncture group, the means of LVIDd and LVIDs15 min after the needles were removed were significantly higher(P < 0.01) than those at 0 min. The means of E/A, EF, FS, and SV significantly decreased(P < 0.01) from 0 to 15 min in the acupuncture group.CONCLUSION: These findings indicate that acupuncture at Neiguan(PC 6) can affect cardiac function by increasing left ventricular diastolic and systolic function in MI rat models, but the effect only lasts for 15 min.
基金Supported by the National Natural Science Foundation of China(No.81774135 and No.81302884)Science and Technology Major Project of Fujian Province(No.2019YZ014004)+1 种基金Natural Science Foundations of Fujian Province(No.2018J01884)Fujian Provincial Health and Family Planning Commission(No.2018-CX-42)。
文摘Objective:To evaluate the effects of Huoxin Pill(活心丸,HXP)on cardiac fibrosis and heart failure(HF)in isoproterenol(ISO)-induced HF rats.Methods:Thirty Wistar rats were randomly divided into 5 groups including control,HF,isosorbide mononitrate(ISMN),HXP low(HXP-L),and HXP high(HXP-H)groups(n=6 for each group)according to the complete randomization method.Rats were pretreated with ISMN(5 mg/kg daily),low concentration of HXP(10 mg/kg daily)or high concentration of HXP(30 mg/kg daily)or equal volume of saline by intragastric administration for 1 week,followed by intraperitoneal injection of ISO(10 mg/kg,14 days),and continually intragastric administrated with above medicines or saline for additional 6 weeks.The effects of HXP treatment on the cardiac function,heart weight index(HWI),pathological changes,and collagen content were further assessed.Moreover,the role of HXP on activation of transforming growth factor-β1(TGF-β1)/Smads pathway was further explored using immunohistochemistry(IHC)and Westernblot assay.Results:HXP treatment significantly alleviated the decrease of ejection fraction(EF)and fractional shortening(FS),while decreased the elevation of left ventricular end-systolic volume(LVESV)in ISO-induced HF rats(P<0.05).Moreover,HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB(CK-MB,P<0.05),as well as pathological changes in ISO-induced HF rats.Further determination indicated that HXP treatment alleviated the elevation of collagenⅠand collagenⅢprotein expression in cardiac tissues of ISO-induced HF rats.Furthermore,HXP treatment significantly down-regulated the increase of TGF-β1 and p-Smad2/3 protein expression in cardiac tissues of HF rats(P<0.05),while did not affect the expression of total Smad2/3.Conclusions:HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-β1/Smad2/3 pathway.
基金Majlesi Branch,Islamic Azad University,Isfahan,Iran for their support
文摘A sensitive electrochemical sensor for the determination of cysteamine(CA) was developed using a modified multiwall carbon nanotube paste electrode(MWCNTPE) with isoproterenol(ISPT) as a mediator.This modified electrode showed very high electrocatalytic activity for the anodic oxidation of CA.Under the optimized conditions,the electrocatalytic peak current showed a linear relationship with CA concentration in the range of 0.3–450.0 mmol/L with a detection limit of 0.09 mmol/L CA.The modified electrode was used for the determination of CA in real samples such as urine and drug samples.
