目的观察瑞舒伐他汀对糖尿病心肌病变的作用。方法选取21只体重在2.0至2.5 kg健康的日本大耳白兔分成三组(每组7只):正常对照组,糖尿病组,糖尿病+瑞舒伐他汀组。糖尿病组和糖尿病+瑞舒伐他汀组采用静脉注射5%葡萄糖及饮用10%葡萄糖的方法制作糖尿病模型。正常对照组和糖尿病组采用普通饲料+饮用水饲养;糖尿病+瑞舒伐他汀组采用普通饲料+饮用水+瑞舒伐他汀(5 mg·kg^-1·d^-1)混合饲养。饲养12周后处死兔,取心肌组织。HE染色观察心肌组织病理学,透射电镜观察心肌超微结构的改变,原位末端标记法(TUNEL)检测心肌细胞凋亡情况,免疫组化染色检测B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、半胱天冬酶(Caspase-3)在心肌组织中的表达。结果电镜观察显示:正常对照组心肌细胞排列整齐且心肌细胞质膜连续完整,内皮细胞结构正常;糖尿病组心肌细胞排列紊乱且质膜模糊断裂,肌原纤维呈灶性溶解;糖尿病+瑞舒伐他汀组的心肌组织细胞排列较整齐且心肌细胞质膜较规则,间质胶原纤维堆积明显减少,排列紊乱,较糖尿病组明显改善。HE染色结果显示:正常对照组心肌细胞排列整齐,细胞核大小一致,胞浆染色均匀;糖尿病组心肌细胞排列紊乱,细胞核大小不一致,并伴有间质纤维化及部分心肌细胞肥大坏死;糖尿病+瑞舒伐他汀组细胞排列相对整齐。TUNEL法检测显示:与正常对照组比较,糖尿病组与糖尿病+瑞舒伐他汀组心肌细胞凋亡率明显增加(P均〈0.01);与糖尿病组比较,糖尿病+瑞舒伐他汀组心肌细胞凋亡率明显降低(P〈0.01)。免疫组化结果显示:与正常对照组比较,糖尿病组和糖尿病+瑞舒他汀组Bax、Bcl-2、Caspase-3阳性表达率增高(P均〈0.01);与糖尿病组比较,糖尿病+瑞舒伐他汀组Bax、Caspase-3阳性表达率降低,Bcl-2阳性?
Objective To observe the effects of rosuvastatin on the myocardial pathological changes of diabetes( DM) in rabbits. Methods twenty-one healthy Japanese white rabbits weighted 2 to 2. 5kg were randomly divided into three groups( n = 7 each) : control group,DM group and DM plus rosuvastatin group. The DM model was established by intravenous injection of 5% glucose and drinking 10% glucose in DM and DM plus rosuvastatin groups. The rats in control group and DM group were fed with regular rat chow and drinkingwater was given. The rats in DM plus rosuvastatin group were fed with rosuvastatin( 5 mg·kg~(-1)·d~(-1)) added to drinkingwater and regular rat chow. After being fed for 12 weeks,the rabbits were killed,and the myocardial tissues were taken. The pathology of myocardial tissues was observed by HE staining; the myocardial ultrastructure was observed by transmission electron microscopy; the myocyte apoptosis was detected by Td T-mediated nick end labeling( TUNEL) method; the expressions of Bcl-2,Bax and Caspase-3 in myocytes were detected by immunohistochemistry staining method. Results The transmission electron microscopy observation showed:( 1) In control group,the myocytes were in alignment; the myocardial plasma membrane maintained continuous integrity; the endothelial cell structure was normal.( 2) In DM group,the myocardial plasma membrane was fuzzy and fracture; the myofibrils presented focal lysis.( 3) In DM plus rosuvastatin group,the myocytes were in approximate alignment; the myocardial plasma membrane maintained approximate continuous integrity; the interstitial collagen fibers accumulation decreased and was improved compared with DM group. HE staining results showed:( 1) In control group,the myocytes were in alignment; the size of the nucleus was uniform; the cytoplasm were evenly stained.( 2) In DM group,the myocytes were nonuniform; the nuclear size is not consistent; the interstitial fibrosis and partial myocytes were hypertrophy and necrosis.(