瑞舒伐他汀抗糖尿病性心肌病的实验研究

Effects of resovastain on prevention of experimental diabetic cardiomyopathy in rats

目的探讨瑞舒伐他汀对大鼠糖尿病性心肌病(DCM)的影响。方法将雄性Wistar大鼠50只随机分为正常对照组(n=8)、DCM组(n=21)和DCM+瑞舒伐他汀组(n=21)。DCM组和DCM+瑞舒伐他汀组腹腔注射链脲佐菌素(STZ)建立DCM大鼠模型,DCM+瑞舒伐他汀组大鼠每天以瑞舒伐他汀20mg/kg灌胃,20周后评价各组的体质量、空腹血糖、空腹胰岛素、甘油三酯及胆固醇。采用彩色多普勒超声心动图仪观测左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)、短轴缩短率(FS)及射血分数(EF),二尖瓣及三尖瓣瓣膜返流情况、二尖瓣口E波最大速度、A波最大速度、E/A的比值、E波减速时间(EDT′)、等容舒张时间(IVRT′)及主动脉血流最大速度(APV)等改变。结果①注射STZ1周后,与正常对照组相比,DCM组和DCM+瑞舒伐他汀组大鼠体质量均显著升高(P均<0.05),空腹胰岛素、血清胆固醇及甘油三酯均明显升高(P<0.01,P<0.05);实验末,与正常对照组相比,DCM组和DCM+瑞舒伐他汀组大鼠体质量显著下降(P均<0.01),空腹胰岛素水平明显降低(P均<0.05),空腹血糖及甘油三酯水平显著升高(P均<0.01),DCM组胆固醇水平显著升高(P<0.01);②超声心动图显示,与正常对照组相比,DCM组和DCM+瑞舒伐他汀组大鼠实验末LVIDd值及LVIDs值明显增加(P均<0.01),二尖瓣和三尖瓣瓣膜返流发生率显著增加(P均<0.05),E/A比值及LVEF降低(P均<0.01);DCM+瑞舒伐他汀组大鼠LVIDd值及LVIDs值较DCM组减小(P均<0.05),房室瓣瓣膜返流发生率减少(P均<0.05),E/A比值及EF升高(P均<0.05)。结论瑞舒伐他汀对DCM大鼠的心功能和心肌重构有一定改善作用。

Objective To investigate effects of resovastain on the cardiac function of diabetic cardiomyopathy（DCM） in rats.Methods 50 Wistar rats 8 week old were randomly divided into three groups： the normal control group（n=8）,the DCM group（n=21） and the DCM plus resovastain group（n=21）.Four weeks later,the DCM animal model was established by intraperitoneal injection of streptozotocin（STZ）,which reached the standard was used for the following procedure;the DCM plus resovastatin group was intragastrically administered with resovastatin（20 mg/kg/d）.After 20 weeks,the role of resovastain in the process of DCM was observed by echocardiography,including left ventricular internal diameter at end-systole（LVIDs）,left ventricular internal diastolic diameter（LVIDd）,ejection fraction（EF,shortening fraction（FS）,valvular regurgitation,Max E wave speed,Max A wave speed,ratio of E/A,E deceleration time（EDT′）,isovolumic relaxation time（IVRT′） and aortic peak velocity（APV）,and also by the detection of biochemical indices,including serum glucose,fasting insulin,triglyceride and cholesterol.Results ①One week after STZ injection,compared with the normal control group,the DCM group and DCM plus resovastatin group had a rise in levels of fasting blood glucose,triglyceride and cholesterol（P〈0.01）.At the end,compared with the normal control group,the body weight in other two groups significantly declined（P〈0.01）and the fasting insulin level also declined（P〈0.05）,while levels of fasting blood glucose and triglyceride increased（P〈0.01）.The level of cholesterol in the DCM group increased（P〈0.01）,while there was no remarkable difference compared with the DCM plus resovastatin group（P〉0.05）.②The DCM group and DCM plus resovastatin group had a significant increase in LVIDd and LVIDs（P〈0.01）,and incidence of valvular regurgitation（P〈0.05）.E/A ratio and EF declined（P〈0.01）.Compared with the DCM group,LVIDs and LVIDd were ameliorated in the DCM plus resovastatin group（P〈0.05）,while the incidence of valvular regurgitation decreased（P〈0.05） and the E/A ratio and EF increased（P〈0.05）.Conclusion Resovastatin can to a certain extent improve cardiac function and myocardial remodeling in DCM rats.