Research On The Protective Effect Of Ginsenoside Rg1 In Diabetic Cardiomyopathy Rats

Background: Diabetic cardiomyopathy is characterized by myocardial dilatation or hypertrophy, and impaired systolic or diastolic function of the left ventricle. The underlying mechanisms for the pathogenesis of diabetic cardiomyopathy are not completely understood. Diverse molecular mechanisms such as oxidative stress, inflammation, myocardial fibrosis, endoplasmic reticulum stress, and apoptotic cell death have all been proposed as potential contributed factors in the pathogenesis of diabetic cardiomyopathy. Cardiocyte apoptosis has been demonstrated in the hearts of diabetic individuals and in streptozotocin(STZ)-induced diabetic rats. Earlier studies have demonstrated ultrastructural evidence of swelling and dilation of endoplasmic reticulum in the diabetic myocardium model. Endoplasmic reticulum stress leads to unfolded protein response that is considered to be an adaptive response aimed at attaining endoplasmic reticulum homeostasis. Further, endoplasmic reticulum stress-induced apoptosis is known to play a key role in the pathogenesis and progression of diabetic cardiomyopathy. Ginsenoside Rg1 is one of the most important ingredients in Panax ginseng. Cardiovascular protective effects of ginsenoside Rg1 have been attributed to its inhibition of cell apoptosis and reduction of oxidative stress. Studies investigating myocardial protective effects of ginsenoside Rg1 have mainly concentrated on hypertrophic cardiomyopathy, acute myocardial infarction, myocardial ischemia/reperfusion. No previous study has investigated the effect of ginsenoside Rg1 on diabetic cardiomyopathy diabetic myocardial damages. The objective of this study was to investigate the effects of ginsenoside Rg1 on diabetic cardiomyopathy in STZ-induced diabetic rats, and to investigate whether the cardioprotective effects of ginsenoside Rg1 were mediated through inhibition of endoplasmic reticulum stress-induced apoptosis.Objective:(1) Gisenoside Rg1 ability to reduce one of the important factors of diabetic heart damage, oxidative stress and apoptosis..(2) The cardioprotective effects of ginsenoside Rg1 were mediated through inhibition of endoplasmic reticulum stress-induced apoptosis.Methods: After the establishment of diabetic rats by intraperitoneal injection of Streptozotocin(STZ, 30 mg/kg), ginsenoside Rg1 was administered for 12 weeks.we observed weight changes,determined cardiac troponin(c Tn)-I、CKMB、TC、TG and FBG levels. Myocardial tissues were harvested to detect myocardial cell apoptosis by Tunel assay,cardial ultrastructural changes by transmission electron microscope and HE staning,oxidative stress-related proteins MDA(Malondialdehyde), SOD(Superoxide Dismutase), GSH(LGlutathione) and CAT(Catalase) activity levels, myocardial fibrosis by Masson staining, and protein expression of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP), Caspase-12, Caspase-3 and bcl-xl protein levels by Western blot and Immunohistochemically.Results:(1) Ginsenoside Rg1 can decrease serum glucose, lipids, enzymes level of diabetic rats, improve myocardial ultrastructural damage, and there is a dose-dependent, high-dose group improved the most obvious.(2) Ginsenoside Rg1 significantly reduced levels of malondialdehyde in serum and myocardial, and increased levels of the antioxidants superoxide dismutase, catalase, and glutathione peroxidase.(3) Treatment with ginsenoside Rg1(10 mg/kg to 20 mg/kg) significantly reduced GRP78, CHOP,,cleaved Caspase-12,Caspase-3 and bcl-xl protein expression in a dosedependent manner. These findings suggest ginsenoside Rg1 appeared to ameliorate diabetic cardiomyopathy by inhibiting ER stress-induced apoptosis in diabetic rats.Conclusions:(1) Ginsenoside Rg1 improve metabolic disorders and myocardial ultrastructure damage in diabetic rats.(2) Ginsenoside Rg1 may play a protective role of diabetes heart by reducing oxidative stress and apoptosis.(3) Cardioprotective effects of ginsenoside Rg1 may be mediated through inhibition of endoplasmic reticulum stress-induced apoptosis. Innovation:(1) In this study, Endoplasmic reticulum stress-induced apoptosis and oxidative stressmay be involved in the pathogenisis of diabetic cardiomyopathy.(2) In this study, Ginsenosid Rg1, as an active ingredient in an extract from the dried roots of Panax notoginseng, may be a new drug for the prevention and treatment of DCM. Ginsenoside Rg1 appeared to ameliorate diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress-induced apoptosis and oxidative stress. In summary, the results of our study suggest that ginsenoside Rg1 treatment was associated with reduced systematic and myocardial oxidative stress in DM rats. Moreover, ginsenoside Rg1 could protect diabetic rats from myocardial injury through attenuation of myocardial apoptosis, possibly by inhibiting the expression of Caspase 3 restoring Bcl-xl and endoplasmic reticulum stress-induced apoptosis. These results indicate that ginsenoside Rg1 may have potential preventative and therapeutic value for cardiovascular injury in DM patients.