The Impact And Underlying Mechanisms Of Ginsenoside Rg1 On Preventing Transverse Aortic Constriction Induced Left Ventricular Hypertrophy

Cardiac hypertrophy is one of the independent risk factors of cardiovascular diseases-related mortality.In general,cardiac hypertrophy—a characteristic of an increase in heart mass—is a poor prognostic sign and is associated with nearly all forms of heart failure.Cardiac hypertrophy is commonly involvement on upregulation of fetal genes,fibrosis,cardiac dysfunction and increased mortality.Cardiac hypertrophy occurs in response to diverse stimulus,such as hypertension,valve diseases,myocardial infarction and genetic mutations.The exact molecular mechanisms leading to cardiac hypertrophy remain undefined but potentially involve multiple pathways.Study of pathphysiological mechanisms contributing to cardiac hypertrophy,and exploring the modern medicine targeting at cardiac hypertrophy has been a hot topic.Ginsenoside,a well-known Chinese medicine,has been used extensively for thousands of years.Ginsenosides Rg1,which is one of the active ingredients of ginseng,has been reported to exert various pharmacological effects on cardiovascular system,including anti-myocardial infarction,anti-arrhythmia,anti-heart failure and anti-cardiac hypertrophy.Recently,Jiang et al.reported that ginsenoside Rg1 inhibited left ventricular hypertrophy in a rat model of abdominal aortic coarctation between the abdominal aorta proximal and the renal bifurcations junction,which involved endogenous Nitric oxide(NO),calcineurin and MAPK signaling.However,the effects and underlying mechanisms of Ginsenoside Rgl on cardiac hypertrophy are still largely unknown.The main object of the present study was to testify the hypothesis that Ginsenoside Rg1 had the effects of anti-cardiac hypertrophy and attenuated cardiac dysfunction.Our study also investigated the underlying mechanisms that associated with anti-cardiac hypertrophy in transverse aortic constriction(TAC)rats model.In this study,there were three gourps:sham group,TAC group,and TAC+ Rgl(10 mg/kg/day,4 weeks).Cardiac functions were evaluated by echocardiography,and we found that Ginsenoside Rgl could inhibit cardiac hypertrophy and alleviated cardiac dysfunction induced by TAC surgery.Contrast with the TAC group,the echocardiography showed that the value of ejection fraction(EF)and fractional shortening(FS)were increased from(59.50±2.89%;32.90±2.08%)to(68.59±1.74%;9.5±1.45%;P<0.05)respectively;left ventricular end-systolic volume(LVvols)decreased from 97.0±9.77 ?l to 67.7±5.16 ?l,p<0.05;left ventricular internal dimension diastole(LVISd)reduced from 4.52±0.20 mm to 3.90±0.13 mm,p<0.05.Hematoxylin and eosin(H&E)staining was used for test the cross-sectional area of cardiomyocytes,and the extent of fibrosis was evaluated by measuring Masson trichrome stained area in whole heart.From the results of H&E and Masson staining,we demonstrated that the extend of fibrosis and the size of cardiomyocytes heightened by TAC,were attenuated by Ginsenoside Rgl.In addition,the expression of procollagen I?procollagen III,and the molecular involvement of angiogenesis were evaluated by immunohistochemisty?western-blotting?and RT-PCR.From the above evaluation,we found that Ginsenosides Rgl had effects of enhancing angiogenesis and decreasing the expression of procollagen I and procollagen III increased by TAC surgery.Thus,we concluded that Ginsenosides Rgl could prevent cardiac hypertrophy and attenuate cardiac dysfunction induced by pressure overload via enhancing angiogenesis.Meanwhile,our study will provide the evidence of using Ginsenosides Rgl for the prevention and therapy in cardiac hypertrophy.