细胞内信息传导改变在大鼠糖尿病心肌病发生中的作用初步研究

梁自文　张忠辉　张平

　　摘要　目的　探讨心肌细胞内DAG-PKC信息传导通路激活在糖尿病性心肌病发病机制中的作用。方法　比较糖尿病大鼠胃饲钒酸盐前后心功能、心肌总DAG含量、胞膜和胞浆PKC活性及心肌形态学变化。结果　糖尿病大鼠心功能明显降低，DAG含量和胞膜PKC活性显著升高，心肌超微结构受损，而胃饲钒酸盐的糖尿病大鼠心功能、心肌DAG含量和PKC活性及超微结构都基本保持正常。结论　DAG-PKC通路激活在糖尿病性心肌病的发生中起着重要作用。
　　关键词　糖尿病性心肌病　钒酸盐　二酰基甘油　蛋白激酸C　大鼠

An Experimental Study on the Biochemical Mechanisms in the
Development of Diabetic Cardiomyopathy

Liang Ziwen, Zhang Zhonghui, Zhang ping
Department of Endocrinology, South-west Hospital,The Third
Military Medical University,Chong Qing,400038

　　Abstract Objective:To study the value of the activation of diacylglycerol (DAG)-protein kinase C (PKC) pathway in the development of diabetic cardiomyopathy.Methods:Comparing the changes of cardias function,total DAG levels,PKC activity of cytomembrane and cytoplasma and ultrastructure of noyocardianh before and after oral administration of vanadate in diabetic rats.Results:In diabetic rats,born the PKC activity from the membranous fraction and total DAG were increased and the cardiac funeton and ultrastructure were deranged,all of these abnormal changes were improved significantly after oral administration of vandate by gavage in diabetic rats.Conclusion:The activation of DAG-PKC pathway plagsa has very important role in the mechanisms of the development of diabetic cardiomyopathy.
Key words Diabetic cardiomyopathy,Vanadate,Diacylglycerol, Protein kinase C, Rat

　　临床工作和动物实验中都观察到糖尿病早期冠状动脉发生病变之前已有心功能降低，表明糖尿病性心肌病的独立存在，其形成与糖尿病所致代谢紊乱有关，但发生机制仍不清楚，本文通过观察糖尿病大鼠8周心肌结构和功能的变化以及与血糖改变的关系，为阐明糖尿病性心肌病的发病机理提供实验依据。
材料和方法
1　模型建立和分组：雄性Wistar大鼠60只，随机取30只腹腔注射链脲佐菌素建立糖尿病模型，另30只仅注射缓冲液作为对照，5天后测血糖并随机将糖尿病和对照大鼠分成4组(各15只)：糖尿病组、对照组、糖尿病+SV组，对照+SV组，其中后2组每天胃饲正钒酸钠(SV，82mg/kg，生理盐水稀释，浓度为0.4%)，持续8周。
2　心功能测定：将麻醉大鼠颈动脉插管至左室腔，生理记录仪测量左室收缩压(LVSP)，左室舒张末压(LVEDP)，左室内压最大上升和下降速率(±dp/dtmax)，留取心血标本以放免法测定胰岛素水平，迅速取下心脏，用冰冷的磷酸缓冲液(不含Ca2+和Mg2+，pH7.4)冲洗，予液氮中冷冻后磨成粉末。
3　抽提并测定总DAG含量：称量组织粉末，加入2ml100%甲醇，匀浆，再加2ml氯仿和1ml蒸馏水于匀

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