Objective To study the roles of abnormal expressions of Caspase-8 and protein kinase C(PKC)-β of cardiomyocytes in the development of the apoptosis of cardiomyocyte in diabetic rat. Methods Rats were divided into 4 groups:(1)normal control (NC, n=37),(2)rats given STZ injection and normal diet(STZ,n= 42), (3) rats fed with high fat and high sngar ( HFS, n= 37), (4)rats given STZ injection and high fat and high sugar diet (type 2 DM, n=64). Plasma glucose, insulin and lipids were detected. At the end of experiment, the animals were sacrificed, and their hearts were examined. Pathological changes were observed and the expressions of Caspase-8, PKC-β mRNA were determined by real time-PCR method; apoptosis was analyzed by flow cytometry. Results (1)The body weight was higher in HFS group than in other three groups, and progressively decreased in type 2 diabetes group. The glucose level was highest in diabetic group, and was similar between groups of HFS and NC. (2)The apoptosis showed tendency to ascend during course of disease in diabetes model group. (3)The expressions of Caspase-8 and PKC-β mRNA were significantly enhanced in diabetes model group than in normal control group, and had a tendency to ascend during the course of disease.(4)The myocardial cells of the diabetic rats were rarified and swelling, fibrosis was observed. (5)At the 16th week, the level of plasma glucose was correlated positively with the expressions of Caspase-8 and PKC-β mRNA. Conclusions The enhancement of expressions of Caspase-8 amd PKC-β may play iportat rols in the pathogenesis of diabetic cardiomyopathy,in which apoptosis of the cardiomyocytes increased.%目的 通过研究糖尿病大鼠心脏中的细胞凋亡,Caspase-8及蛋白激酶C(PKC)-β的表达来探讨糖尿病心肌病(DCM)的组织学改变与细胞分子水平改变的相互关系.方法 实验大鼠分为4组:(1)糖尿病组,64只,用高糖高脂饲料喂养,予链脲佐菌素(STZ)30 mg/L一次性腹腔注射复制糖尿病模型.(2)正常对照组,37只,饲以普通饲料,腹腔注射柠檬酸盐缓冲液代替STZ.(3)STZ组,42只,饲以普通饲料,腹腔注射STZ.(4)高糖高脂组,37只,饲以高糖高脂饲料,腹腔注射柠檬酸盐缓冲液.在不同时段,抽样检查动物:观察心脏病理组织学变化;用实时荧光定量(PCR)等技术检测心肌Caspase-8及PKC-β的表达;用流式细胞术检测心肌的凋亡.比较不同组间的差异.结果 (1)造模型成功后,糖尿病组大鼠体质量较对照组明显下降(P＜0.05),且随着病程的进展呈下降趋势.高糖高脂组体质量一直较高,各时间段无明显改变.糖尿病组的血糖一直都高于对照组、STZ组及高糖高脂组(P＜0.05);高糖高脂组和对照组血糖差异无统计学意义.(2)糖尿病组细胞凋亡有随着病程延长而增高的趋势.(3)造模型成功后,Caspase-8、PKC-β的表达,糖尿病组高于对照组,而且有随着病程的延长增加的趋势.(4)糖尿病组发生心肌肥大、纤维化,随着病程的延长,病变有逐渐加重的病理特点.(5)相关分析提示,糖尿病组16周时,血糖和心肌细胞凋亡与Caspase-8、PKC-β的表达呈正相关.结论 Caspase-8表达失衡与DCM的发病有关.PKC-β在DCM中起到了一定的作用.高血糖在DCM的发病中起重要的作用.
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