| Background:Myocardial ischemia is a common cardiovascular disease that causes irreversible myocardial injury resulting extremely high morbidity and mortality worldwide.Ischemic myocardial injury can cause myocardial fibrosis(MF),leading to myocardial systolic and/or diastolic dysfunction,and ultimately heart failure.Ginseng is used in the treatment of cardiovascular diseases and plays a beneficial role in cardiomyopathy.Latest studies have shown that the main active component of ginseng is ginsenosides,and different ginsenosides have different pharmacological activities.With some ginsenosides might have more potent pharmacological effects,meanwhile,the content of these ginsenosides in ginseng is very low,causing difficulties in developing and utilizing.Ginsenoside Re has a high content in ginseng and it is easy to be isolated and purified.However,it has not been reported whether Ginsenoside Re can reduce ischemic myocardial injury,reduce MF and improve cardiac function in ischemic cardiomyopathy.Aim:This study was designed to investigate the protective effect of Ginsenoside Re on isoproterenol-induced myocardial injury and its mechanism in inhibiting isoproterenolinduced MF and alleviating heart failure in rats.Methods:(1)Fifty six Wistar male rats were randomly divided into control,isoproterenol and Ginsenoside Re(5,20 mg/kg)groups.Rats in control and isoproterenol groups were orally administrated with 0.5% sodium carboxymethyl cellulose(CMC-Na)daily for 7 days.While animals in Ginsenoside Re groups were intragastrically treated with Ginsenoside Re at doses of 5 or 20 mg/kg,respectively,daily for 7 days.Isoproterenol(20 mg/kg)was dissolved in normal saline and subcutaneously injected to rats at an interval of 24 h for 2 days(on 6th and7 th day)to induce myocardial ischemic injury,while the control groups was subcutaneously injected with normal saline of the same volume.24 hours after the last isoproterenol injection,troponin T level and creatine kinase-MB(CK-MB)activity were assayed.Histopathological examination of heart tissues was performed.The levels of malondialdehyde(MDA)and glutathione(GSH)in heart tissues were measured.The nuclear factor erythroid 2-related factor 2(Nrf2)content in nucleus and the proteins of glutathione cysteine ligase catalytic subunit(GCLC)and glutathione cysteine ligase modulatory subunit(GCLM)in heart tissues were assayed by western blotting method.(2)Sixty Wistar male rats were randomly divided into control,isoproterenol and Ginsenoside Re(5,20 mg/kg)groups.Isoproterenol was dissolved in normal saline and injected subcutaneously to rats at a dose of 5 mg/kg,once daily for 7 consecutive days to induce experimental myocardial fibrosis and heart failure.Meanwhile,The animals in Ginsenoside Re groups were orally treated with Ginsenoside Re at doses of 5 or 20 mg/kg,rats in control and isoproterenol groups were orally administrated with 0.5% CMC-Na of the same volume,respectively,daily for 4 weeks.The cardiac function was measured using a hemodynamic analyzing system.Heart weight index and hydroxyproline were assayed.Sirius red staining was performed to observe the myocardial tissue fibrosis degree.The content of transforming growth factor ?1(TGF-?1)in serum was assayed by ELISA.Smad3,p-Smad3 and collagen type I in heart tissues were assayed by western blotting method.Results:(1)In the model of rat myocardial ischemic injury,treatment with Ginsenoside Re at a dose of 5,20 mg/kg reduced troponin T level and CK-MB activity of rats subjected to isoproterenol.The cardioprotective effect of Ginsenoside Re was further confirmed by histopathological examination which showed that Ginsenoside Re attenuated the necrosis,inflammatory cells infiltration,and myofibrillar fracture.Ginsenoside Re inhibited the increase of MDA content and the decrease of GSH in heart tissues.Moreover,the Nrf2 content in nucleus and the expressions of GCLC,GCLM were significantly increased in the animals treated with Ginsenoside Re.(2)In the model of rat myocardial fibrosis and heart failure,isoproterenol caused decreases in values of the positive and negative maximal values of the first derivative of left ventricular pressure(ądp/dt max),left ventricular systolic pressure(LVSP)and a significant increase in the left ventricular end diastolic pressure(LVEDP)as compared with the rats in the control group.Compared with the isoproterenol group,Ginsenoside Re treatment ameliorated changes of LVSP,ądp/dt max and LVEDP.Isoproterenol enhanced the heart weightindex,the collagen fibers and the content of hydroxyproline in the hearts.Ginsenoside Re partially inhibited the isoproterenol-induced increase of the heart weightindex,the collagen fibers and the hydroxyproline content.Ginsenoside Re administration also resulted in a decreased TGF-?1 level in serum and decreased expressions of p-Smad3,collagen type I in heart tissue.Conclusions:Ginsenoside Re plays role in attenuating isoproterenol-induced myocardial injury,the mechanism is related to the regulation of Nrf2-mediated GCLC and GCLM expression,which leads to the improvement of antioxidant function.Also,the mechanism of Ginsenoside Re improving the isoproterenol-induced MF and heart function is related to the regulation of TGF-?1/Smad3 pathway. |
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