Gardenoside alleviates diabetic cardiomyopathy via inhibiting VPO1/ERK1/2 signaling pathway to improve myocardial apoptosis in rats / 中国临床药理学与治疗学

ABSTRACT

AIM: To investigate the effect of geniposide (GE) on diabetic cardiomyopathy and its mechanism. METHODS: Twenty-four adult male SD rats were randomly divided into three groups Control group (n=8), DCM group (n=8) and DCM+ GE group (n=8). The diabetic cardiomyopathy model was established by high fat diet combined with streptozotocin (STZ), and H9C2 injury model was induced by hypochlorite (HOCl). After 12 weeks of intervention, the histopathological changes of heart were observed by HE and Masson staining, the level of cardiomyocyte apoptosis was detected by TUNEL staining, and the expression levels of VPO1/ERK1/2 signal pathway and apoptosis-related proteins were detected by immunohistochemistry and Western blot. The changes of ERK1/2, p-ERK1/2, Bcl-2 and Bax protein expression in cardiomyocytes were detected by Western blot after HOCl stimulation. After administration of ERK1/2 inhibitor U0126, the protein expression levels of ERK1/2, p-ERK1/2, Bcl-2 and Bax were detected again by Western blot assay. RESULTS: Compared with the control group, the arrangement of myocardial fibers was disordered and the content of myocardial collagen was significantly increased in DCM group by HE and Masson staining, while the myocardial injury was significantly improved in DCM+GE group (P<0.05). Compared with the control group, the apoptotic rates of cardiomyocytes and the ratio of Bax/Bcl-2 in DCM group were remarkably increased, while the myocardial apoptosis in DCM+GE group was significantly improved (P<0.05). The results of immunohistochemistry and Western blot showed that the expression of VPO1 and p-ERK1/2 was increased in DCM group, while the expression level of VPO1 and p-ERK1/2 was inhibited in DCM+GE group (P<0.05). When H9C2 cells were stimulated with HOCl, the expression of p-ERK1/2 and the ratio of Bax/Bcl-2 were both increased as compared with the control group, while the expression level of p-ERK1/2 and the ratio of Bax/Bcl-2 were decreased after the addition of ERK1/2 inhibitor U0126 (P<0.05). CONCLUSION: Geniposide alleviates the diabete-induced myocardial injury by suppressing cardiomyocyte apoptosis via inhibiting VPO1/ERK1/2 signal pathway.