Beneficial Effects of Atorvastatin on Ventricular Remodeling Cardiac Function after Acute Myocardial Infarction in Streptozotocin-induced Diabetic Rat Model

Objective Our preliminary studies has shown that after ligation of left anterior descending coronary artery,diabetic rats had worse left ventricular (LV) function and accelerated LV remodeling than non-diabetic ones,and four weeks after acute myocardial infarciton (AMI),the myocardial fibrosis was increased significantly in the diabetic.In the present study,our aim was to investigate the beneficial effects of atorvastatin on ventricular remodeling after AMI in Streptozotocin-induced diabetic rat models.Methods 75 male Sprague-Dawley (SD) rats underwent induction of diabetic animal models were randomized into three groups:atorvastatin (20 mg·kg-1·d-1 was administered via direct gastric gavage 24 hours after the ligation,Group A,n=30),AMI control group (distilled water of the same volume was given by gastric gavage,Group MI,n=30) and sham group (administered with distilled water too,Group S,n=15),respectively.All diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ,65 mg/kg),and 10 weeks later after the induction,AMI models were made with the ligation of left anterior descending coronary artery.After four weeks,the effects of atorvastatin were evaluated by detecting changes of the hemodynamics,and then all the rats were killed and their hearts were taken out to detect the changes of heart to body weight ratios and HE staining.Picric-Sirius Red Polarimetry was used to detect the typeⅠand type Ⅲ collagen volume fraction (CVF).Immunohistochemiistry was used to dectet the expressions of MMP-2 and TIMP-2.Western blot was used to detect the expressions of TGFβ1 in protein level.Result (1) There were no significant differences between groups in levels of serum lipids.(2)Contrasted to the Group MI,heart to body weight ratios,typeⅠCVF,Ⅲ CVF and Ⅰ/Ⅲ ratios in NIZ were decreased significantly in Group A,but higher than Group S.Immunohistochemiistry and Western blot showed that the expression levels of MMP-2 and TGFβ1 and MMP-2/TIMP-2 ratios in Group A were all significantly lower than those of Group MI,but that of TIMP was increased significantly.(3)Compared with the Group MI,the maximum of left ventricular pressure (LVPmax),the maximum and minimum values of first derivative of left ventricular pressure over time (dp/dt max and dp/dt min),mean arterial blood pressure (MABP) in group A were significantly increased,however,the minimum of LVP (LVPmin),the constant of isovolumic pressure decay(Tau) and left ventricular end diastolic pressure (LVEDP) were significantly decreased.Conclusion Prolonged treatment with atorvastatin ameliorates early LV remodeling and improves cardiac function after AMI in Streptozotocin-induced diabetic rat models.Atorvastatin can attenuate myocardial interstitial collagen remodeling in non-infarction zone of the left ventricle,the mechanisms of which may be independent of its lipid-lowering and associated with its effects of down-regulating MMP-2,TGFβ1 and MMP-2/TIMP-2 ratios,and up-regulating TIMP-2.