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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阳性表达率增高(P均<0.01)。结论瑞舒伐他汀可以改善糖尿病兔心肌组织细胞病理改变及超微结构的改变,抑制心肌细胞凋亡,其机制可能与细胞因子的调控有关。
Objective To observe the effect of rosuvastatin on diabetic cardiomyopathy. Methods Twenty-one Japanese white rabbits weighing from 2.0 to 2.5 kg were divided into three groups (n = 7): normal control group, diabetic group and diabetic + rosuvastatin group. Diabetes mellitus group and diabetes mellitus + rosuvastatin group were injected with 5% glucose and 10% glucose to make diabetic model. The normal control group and diabetic group were fed with ordinary feed + drinking water. The normal diet + drinking water + rosuvastatin (5 mg · kg -1 · d -1) were used in the diabetic + rosuvastatin group Mixed feeding. Rabbits were sacrificed after 12 weeks of feeding, myocardial tissue was taken. Myocardial histopathology was observed by HE staining. The changes of myocardial ultrastructure were observed by transmission electron microscopy. Cardiomyocyte apoptosis was detected by TUNEL. Bcl-2 (Bcl-2) was detected by immunohistochemistry ), Bcl-2-related protein B (Bax) and Caspase-3 in myocardium. Results Electron microscopy showed that the myocardial cells in the normal control group were arranged neatly and the plasma membrane of the myocardial cells were continuously intact and the endothelial cells were normal in structure. Cardiomyocytes in the diabetic group were disordered and the plasma membrane was blurryly ruptured with myofibrillar fibrosis dissolving. Diabetes mellitus + rosuvastatin Compared with the diabetic group, the myocardial cells in the group were arranged neatly and the plasma membrane of myocardial cells was more regular. The accumulation of interstitial collagen fibers was significantly reduced and disordered. The results of HE staining showed that the myocardial cells in normal control group were arranged neatly, the nucleus size was uniform and the cytoplasm was stained uniformly. The myocardial cells in diabetic group were disordered, the nucleus size was inconsistent, accompanied by interstitial fibrosis and hypertrophy and necrosis of some cardiomyocytes. Shuvastatin group cells arranged relatively neatly. TUNEL assay showed that compared with the normal control group, the apoptosis rate of cardiomyocytes in diabetic group and diabetic + rosuvastatin group was significantly increased (all P <0.01). Compared with diabetic group, the apoptosis of myocardial cells in diabetic + rosuvastatin group Mortality was significantly lower (P <0.01). The results of immunohistochemistry showed that compared with the normal control group, the positive rates of Bax, Bcl-2 and Caspase-3 in diabetes mellitus group and diabetes mellitus group were significantly increased (all P <0.01); Compared with diabetic group, The expression of Bax and Caspase-3 in the statin group decreased and the expression of Bcl-2 protein increased (all P <0.01). Conclusion Rosuvastatin can improve the pathological changes and ultrastructural changes of myocardial cells in diabetic rabbits and inhibit cardiomyocyte apoptosis, which may be related to the regulation of cytokines.