Tanshinon II A attenuates diabetic cardiomyopathy by down-regulation of mTOR/P70S6K signaling pathway

Introduction: To verify whether tanshinone II A (Tan II A) could inhibit the development of diabetic cardiomyopathy (DCM) by blocking the mTOR/P70S6K signaling pathway. Material and Methods: Diabetes mellitus (DM) on Wistar Rats were induced by streptozocin (STZ). Sixty four DM rats were randomly divided into 4 groups: (1) Normal control (NC) group; (2) DM group; (3) Tan II A group; (4) MHY-1485 group. After 6 weeks of intervention, cardiac function was assessed by echocardiography. Serum levels of TNF-alpha, IL-6 and IL-1 beta were measured with Elisa method. Masson trichrome stain was used to evaluate cardiac fibrosis and electron microscope was used to test the cardiomyocytes ultrastructure. Western blotting was employed to investigate the expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, p-mTOR and p-P70S6K. Gelatin zymography was used to detect the activity of MMP2 and MMP-9. Results: Compared with the DM group, Tan II A effectively improved cardiac function of contraction (P<0.05), decreased serum inflammatory factor levels (P<0.05), attenuated cardiac fibrosis, increased the expression and activity of MMP-2/9, and blocked mTOR/P70S6K signaling pathway (P<0.05). Meanwhile, MHY-1485 reversed the effect of Tan II A (P<0.05). Conclusion: Tan II A attenuated DCM by down-regulation of mTOR/P70S6K signaling pathway.