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背景:糖尿病蛋白质非酶糖化过程中可产生大量的氧自由基,同时伴有一氧化氮合成下降,致使细胞内钙增加,胞内致密颗粒排空、激活胞内酶而启动细胞凋亡的发生。目的:观察非酶糖化抑制剂氨基胍对糖尿病大鼠心肌细胞凋亡及其心功能的影响。设计:完全随机分组设计,对照实验。单位:锦州医学院药理学教研室。材料:实验于2002-09/2003-03在锦州医学院中心实验室完成。选用2月龄雄性SD大鼠54只。方法:选36只大鼠按60mg/kg尾静脉一次性注射链脲佐菌素溶液造成糖尿病模型,将血糖>16.7mmol/L的大鼠定为糖尿病造模成功。将模型鼠分为2组:糖尿病组和氨基胍治疗组各18只,每组又分12周8只和12周10只。另18只大鼠为对照组,分为2个时间点:12周8只,24周10只。各组大鼠分别饲养12和24周,其中氨基胍治疗组按150mg/(kg·d)将氨基胍于饮水中喂养。其余2组正常饲养。计算心脏质量指数[心脏(mg)/体质量(g)]。取左室心肌组织块,进行透射电镜观察。原位末端标记法染色,用10×10目镜方格系统计数10个视野原位末端标记法阳性细胞核数,取其均值。主要观察指标:糖尿病大鼠心脏结构和功能改变过程中是否存在心肌细胞凋亡以及氨基胍的作用。结果:实验过程因大鼠死亡和造模失败脱失8只,最终进入结果分析46只。①心脏质量指数:糖尿病组12和24周时明显高于对照组和氨基胍治疗组(P<0.05～0.01)。②左室内压最大下降和上升速率:糖尿病组12和24周时明显低于对照组和氨基胍治疗组(P<0.05～0.01)。③左室内压最大上升速率:糖尿病组24周时明显低于12周时(P<0.05)。④细胞凋亡数目:糖尿病组明显高于对照组和氨基胍治疗组(P<0.01),糖尿病组24周时明显高于12周时(P<0.01)。⑤心肌细胞超微结构观察结果:糖尿病组心肌组织内可见凋亡的心肌细胞。结论:心肌细胞凋亡在糖尿病心肌病发生发展过程中有重要影响,氨基胍可有效减少心肌细胞凋亡,改善心肌病理形态学异常。
BACKGROUND: Diabetic protein non-enzymatic glycation process can produce a large number of oxygen free radicals, accompanied by decreased synthesis of nitric oxide, resulting in increased intracellular calcium, intracellular dense particles emptying, activation of intracellular enzymes and start the occurrence of apoptosis. Objective: To observe the effect of aminoguanidine, a non-enzymatic glycation inhibitor, on cardiomyocyte apoptosis and cardiac function in diabetic rats. Design: Complete randomized block design, control experiment. Unit: Jinzhou Medical College Department of Pharmacology. Materials: The experiment was performed at Jinzhou Medical College Central Laboratory from September 2002 to March 2003. 54 male SD rats of 2 months old were selected. Methods: A total of 36 rats were injected with streptozotocin solution at a dose of 60mg / kg into the tail vein to induce the diabetic model. Rats with blood glucose> 16.7mmol / L were considered as diabetic models. The model rats were divided into 2 groups: 18 in diabetic group and aminoguanidine group, 8 in each group and 10 in 12 weeks. Another 18 rats as control group, divided into two time points: 12 weeks 12, 24 weeks 10. The rats in each group were kept for 12 and 24 weeks, respectively. The aminoguanidine group was fed with 150g / (kg · d) aminoguanidine in drinking water. The remaining two groups were kept normally. Calculate the heart mass index [heart (mg) / body mass (g)]. Take left ventricular myocardial tissue block, transmission electron microscopy. In situ end labeling staining, with 10 × 10 eyepiece grid system counts 10 fields of end-of-core labeling method of nuclei, whichever is the mean. MAIN OUTCOME MEASURES: Myocardial cell apoptosis and the role of aminoguanidine in the changes of cardiac structure and function in diabetic rats. Results: During the experiment, 8 rats died of the death and the failure of modeling, finally entering the result analysis of 46 rats. ① Heart mass index: The diabetic group was significantly higher than the control group and aminoguanidine group at 12 and 24 weeks (P <0.05 ~ 0.01). (2) The maximum descending and rising rate of left ventricular pressure were significantly lower in diabetic group than those in control group and aminoguanidine group at 12 and 24 weeks (P <0.05 ~ 0.01). (3) The maximal rate of rise of left ventricular pressure was significantly lower in diabetic group at 24 weeks than that in 12 weeks (P <0.05). ④ The number of apoptotic cells in diabetes mellitus group was significantly higher than that in control group and aminoguanidine group (P <0.01). Diabetes mellitus group was significantly higher at 24 weeks than at 12 weeks (P <0.01). ⑤ ultrastructural observation of myocardial cells: myocardial cells in diabetic group can be seen apoptotic cardiomyocytes. Conclusion: Cardiomyocyte apoptosis plays an important role in the development of diabetic cardiomyopathy. Aminoguanidine can effectively reduce cardiomyocyte apoptosis and improve myocardial pathomorphology.