Ginsenoside Re Can Inhibit Left Ventricular Hypertrophy In Spontaneously Hypertensive Rats Via Akt/mTOR Signaling Pathway

Objective: To clarify the protective effect of ginsenoside Re(G-Re)on left ventricular hypertrophy in spontaneously hypertensive rats(SHR),and further study the effect of G-Re on Apelin/APJ system and the regulation of Akt/m TOR autophagy pathway in the process of SHR left ventricular hypertrophy.Methods: Taking SHR as the research object,14 week old male SHRs were randomly divided into five groups: SHR group(model group),G-Re 10 group(G-Re low dose group,SHR + G-Re 10 mg/kg),G-Re 20 group(G-Re medium dose group,SHR + G-Re 20 mg/kg),G-Re 40 group(G-Re high dose group,SHR + G-Re 40 mg/kg),captopril group(positive control group,SHR + captopril 30 mg/kg),There were 10 rats in each group,and another 10 male Wistar-Kyoto rats(WKY rats)were taken as the normal control group(WKY group).The normal control group and model group were given isovolumic double distilled water by gavage,and each administration group was given corresponding drugs by gavage once a day for 12 weeks.The systolic blood pressure of rats was measured by noninvasive rat tail blood pressure meter at a fixed time every week;After 12 weeks of administration,the left and right ventricles of rats were separated,and the left ventricular hypertrophy index and the weight ratio of left and right ventricles were calculated;Left ventricular posterior wall(diastole),left ventricular internal diameter(diastole),relative wall thickness,stroke volume,fractional shortening,ejection fraction were measured by echocardiography;H&E staining and Masson staining were used to evaluate the hypertrophy and fibrosis of rat cardiomyocytes;Western Blotting analyze then protein expression of APJ,β-arrestin2,Beclin1,p62,Akt,P70S6 K and p-m TOR in myocardial tissue.Results: The systolic blood pressure of WKY rats was basically stable in the normal range,while the systolic blood pressure of SHR increased with the increase of week age.Compared with WKY group,left ventricular hypertrophy index and left and the weight ratio of left and right ventricles in SHR group were significantly increased;The left ventricular posterior wall(diastole)thickened significantly,left ventricular internal diameter(diastole)decreased,relative wall thickness increased significantly,and the stroke volume,fractional shortening and ejection fraction decreased significantly;Cardiomyocytes were enlarged,myocardial fibers were arranged disorderly,and a large number of collagen fibers were accumulated around blood vessels and stroma of myocardial tissue;The protein expression of APJ,β-arrestin2,Beclin1,Akt,m TOR,p-m TOR and P70S6 K in myocardial tissue was up-regulated,and the protein expression of p62 was down-regulated.After 12 weeks of treatment with GRe and captopril,compared with SHR group,G-Re and captopril could reduce the blood pressure of SHR,decrease left ventricular hypertrophy index and the weight ratio of left and right ventricles in SHR,reduce the thickness of left ventricular posterior wall(diastole),expand left ventricular internal diameter(diastole),reduce relative wall thickness,and increase the stroke volume,fractional shortening and ejection fraction of SHR;G-Re and captopril could reduce the cross-sectional area of cardiomyocytes,make the cardiomyocytes arranged orderly,and the cell morphology tended to be normal,and the deposition of collagen fibers around blood vessels and stroma in myocardial tissue was reduced;G-Re and captopril could significantly down-regulate the protein expression of APJ,β-arrestin2,Beclin1,Akt,P70S6 K and p-m TOR,and up-regulate the protein expression of p62 significantly in myocardial tissue.Conclusion: G-Re can inhibit left ventricular hypertrophy in spontaneously hypertensive rats,and its mechanismis related to G-Re inhibiting APJ receptor activation and blocking β-arrestin2-mediated Akt/m TOR signaling.