摘要
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： Oxygen-derived free radicals are produced during non-enzymatic glycosylation of diabetic protein and accompanied with decrease in nitrogen monoxide （NO） synthesis so as to cause the calcium increase in cell,evacuation of pykno-granule and apoptosis induced by activating endoenzyme.OBJECTIVE： To observe the effects of non-enzymatic glycosylation inhibitor-aminoguanidine on apoptosis of cardiac myocyte and cardiac function in diabetic rats.DESIGN： Completely randomized grouping design and controlled study.SETTING： Pharmacological Department of Jinzhou Medical College.MATERIALS： The experiment was completed at the Central Laboratory of Jinzhou Medical College between September 2002 and March 2003. Totally 54 male SD rats with 2-month old were selected.METHODS： Totally 36 rats were selected to establish diabetic model 60 mg/kg of streptozotocin were injected into the caudal vein. If blood glucose of rats was more than 16.7 mmol/L, the establishment of diabetic model was successful. Model rats were divided into diabetes group and aminoguanidine （AG） group with 18 in each group. Rats in each group were also divided into two 12-week groups with 8 and 12 respectively. Another 18 rats were determined as the control group at 2 time points： 12 weeks （n=8） and 24 weeks （n=10）. Rats in each group were fed for 12 and 24in other two groups. Calculation of mass index was [heart （mg）/body mass （g）]. Myocardial tissue of left ventricle was taken out and observed with transmission electron microscope and then stained with in situ end-labeling （ISEL） method. Number of positive nucleus was counted with 10 × 10 ocular lens check system and with 10 fields ISEL method; meanwhile, their average was obtained.MAIN OUTCOME MEASURES： Whether there was apoptosis of cardiac cell and the effect on AG in changes of cardiac structure and function of diabetic rats or not.RESULTS： Eight rats were lost during the experiment because of death mass： That of rats in the 12-week and 24-week diabetic group was higher decrease and increase rate of pressure in left ventricle： That of rats in the 12-week and 24-week diabetic group was lower than that in the control in left ventricle： That in 24-week diabetes group was obviously lower than diabetic group was obviously more than that in AG group （P 〈 0.01）, and that in 24-week diabetes group was obviously more than that in 12-week Apoptosis could be observed in myocardial cell in diabetic group.CONCLUSION： Apoptosis of myocardial cell plays an important role in the development of heart failure in diabetic rats. AG can reduce the apoptosis of myocardial cell and decrease the myocardial pathomorphological abnormality.
出处
《中国临床康复》
CSCD
北大核心
2005年第39期164-165,共2页
Chinese Journal of Clinical Rehabilitation
