Activation of Cannabinoid Receptor Type II by AM1241 Ameliorates Myocardial Fibrosis via Nrf2-Mediated Inhibition of TGF-β1/Smad3 Pathway in Myocardial Infarction Mice

摘要: Aims: Myocardial interstitial fibrosis is a major histologic landmark resulting in cardiac dysfunction after myocardial infarction (MI). Activation of cannabinoid receptor type II (CB2 receptor) have been demonstrated to reduce hepatic cirrhotic rat. However, the anti-fibrotic effect CB2 activation infarcted hearts was still unclear. In this study, we aimed investigate effects selective agonist AM1241 on post MI mice. Methods: Echocardiograph conducted assess function. Fibrosis markers such as I and III collagen, fibronectin, Plasminogen activator inhibitor(PAI)-1 tissue inhibitor metalloprotease(TIMP)-1 were examined by Western blot, while collagens directly observed Sirius-red staining. Primary cultured fibroblasts(CFs) subjected hypoxia/serum deprivation (H/SD) injury simulate ischemic conditions vivo . Nrf2 siRNA applied explore role TGF-β1/Smad3 pathway process. Results: Echocardiography showed that significantly improved function, suppressed expression collagen III, PAI-1 TIMP-1 mice with MI. fibroblasts H/SD injury, reduced elevated levels α-SMA, which partially abrogated transfection. Furthermore, not only activated accelerated translocation nucleus, but also inhibited TGF-β1/ Smad3 an dependent manner. Conclusion: alleviated via -mediated down-regulation pathway, suggested might represent promising target for retarding