| Objective: Diabetic cardiomyopathy is one of the main causes of death in patients with type 2 diabetes.Clinical manifestations of diabetic cardiomyopathy are ventricular diastolic and systolic dysfunction,even the intractable heart failure,and there is no novel therapeutic method.Myocardial fibrosis is one of the main pathological features of diabetic cardiomyopathy.The aim of this study is to investigate the effects of atorvastatin on myocardial fibrosis and the Rho A/ROCK signaling pathway,providing a theory for treating diabetic cardiomyopathy.Methods: Female Sprague-Dawley(SD)rats were randomized into two groups,rats were given standardized diet as the normal group,rats were injected with low dose(30mg/kg)streptozotocin(STZ)in enterocoelia and sequentially given a high-fat diet as the experimental group.At week 10,fasting insulin(FINS),fasting blood glucose(FBG),total cholesterol(TC)and triglyceride(TG)were measured.Diabetic rats were randomly divided into two groups: diabetic group(DM)and atorvastatin group(DA).Blood glucose and body weight were recorded every week.At week 21,LVPWs,LVPWd,LVIDs,LVIDd and LVEF were valuated by echocardiography.FINS,FBG,TG,TC and Hb A1 c were measured.Then rats were killed,the heart morphology were observed with hematoxylin-eosin staining and masson staining.Type-Ⅰ procollagen and type-Ⅲ procollagen m RNA was evaluated by real-time PCR.The levels of active Rho A protein expression and p-MYPT1 protein expression were detected by Western blotting.Results:1 Changes of body weight:At week 10,the weight of rats in high-fat diet group was significantly higher than that in normal-diet group(P<0.05).At week 21,the weight of diabetic rats was significantly higher than the control group rats(P<0.01).There was no significant differences between diabetic group rats and treated with atorvastatin rats(P>0.05),while the body weight of treated with atorvastatin rats was lower than the control rats(P<0.01).2 Parameters of cardiac function:Compared with NC group,untreated diabetic hearts showed significantly increased LVPWs,LVPWd,LVIDs and LVIDd,whereas LVEF were obviously decreased(P<0.01).Treatment with atorvastatin decreased LVPWs,LVPWd,LVIDs and LVIDd increased LVEF(P<0.01)in comparison with diabetic rats,while increased LVPWs,LVPWd,LVIDs and LVIDd decreased LVEF(P<0.01)compared with control rats.3 Changes of biochemical parameters:At week 10,diabetic rats had higher values of FBG,FINS,TG and TC compared with those in control rats(P<0.01).At week 21,the levels of FBG,FINS,TC,TG and Hb A1 c of the DM group were significantly higher compared with NC group(P<0.01).There were no differences in the index between DM group and DA group(P>0.05),and the levels of FBG,FINS,TC,TG and Hb A1 c in DA group rats were higher than those in NC group rats(P<0.01,P<0.05).4 HE staining:In the NC group,the myocardial cells were arranged in order and the structure was clear,and there was a mall amount of fibroblast in the cardiac matrix.Disordered arrangement of myocardial cells and obviously increased fibroblasts cloud be observed in the DM group.While the pathological changes of DA group were slighter than that of DM group.5 Masson staining:Compared with the control group,the collagen fibers in the myocardium of the diabetic rats were significantly higher(P<0.01).Treated with atorvastatin decreased the level of collagen fibers in comparison with untreated rats(P<0.01).There were no significant differences of the collagen fiber between NC group and DA group(P>0.05).6 The result of type-Ⅰ procollagen,type-Ⅲ procollagen and hydroxyproline(HYP): Type-Ⅰ procollagen,type-Ⅲ procollagen m RNA and HYP content in DM group was significantly higher than that in NC group and DA group(P<0.01).Type-Ⅰ procollagen,type-Ⅲ procollagen m RNA and HYP content in DA group was significantly lower than that in diabetic group(P<0.01),and there were no significant differences in these index compared with NC group(P>0.05).7 Protein expression in myocardial tissue:The levels of active Rho A and p-MYPT1 were significantly raised in the hearts of DM group compared with those of NC group(P<0.05),while it was markedly suppressed by the intervention of atorvastatin(P<0.05).The level of active Rho A and p-MYPT1 were a little bit higher in the hearts of DA group compared with those of NC group(P<0.05).Conclusions:1 Rho A/ROCK signaling pathway in myocardial tissue was activated by hyperglycemia,leading to increased collagen synthesis and myocardial fibrosis.2 Rho A/ROCK signaling pathway was significantly inhibited by treated with atorvastatin,and cardiac function and myocardial fibrosis were improved.3 The cardioprotective effects of Atorvastatin may be partly associated with inhibition of Rho A/ROCK signaling pathway in myocardial tissue. |
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