糖尿病大鼠肾脏蛋白激酶C活性和血管内皮细胞生长因子的关系  

Study of PKC activity and expression of VEGF in renal of diabetic rats

作　　者：徐静[1] 易兰兰[1] 张春虹[1] 王俊宏[1] 戴信刚[1] 曹会芳[1] 

机构地区：[1]西安交通大学医学院第二附属医院内分泌科,陕西西安710004

出　　处：《中国现代医学杂志》2006年第12期1775-1778,共4页China Journal of Modern Medicine

基　　金：陕西省自然科学基金资助项目(No.2003C234)

摘　　要：目的研究糖尿病大鼠肾小球中蛋白激酶C(PKC)活性变化和血管内皮细胞生长因子(VEGF)表达的动态变化,探讨两者之间相互关系以及它们与糖尿病肾病(DN)发生发展之间的关系。方法用链脲佐菌素制备糖尿病大鼠实验模型,将大鼠随机分为正常对照组(N)、糖尿病2周组(DM2)和糖尿病4周组(DM4)。断头处死,分离肾小球,提取纯化胞浆及胞膜蛋白,利用(γ-32P)ATP底物磷酸化的方法检测胞浆及胞膜PKC活性。用免疫组化和400倍光镜检测VEGF在各组大鼠肾脏的表达。结果糖尿病大鼠肾小球细胞内总的PKC活性与对照组差异无显著性,胞浆PKC活性略有下降,相差不显著;肾小球细胞膜PKC活性明显高于正常对照组,膜结合PKC百分比显著增加,且细胞膜PKC活性与肾脏肥大指数及Ccr呈正相关。糖尿病组VEGF的表达多于正常对照组。肾小球细胞膜PKC活性与肾组织VEGF的表达正相关。结论高血糖慢性刺激可引起肾小球PKC活性增高,并诱导VEGF的高表达。PKC的激活在DN的发生发展中发挥着重要的调控作用。[Objective] To explore the protein kinase C（PKC） activity and the expression of vascular endothelial growth faetor（VEGF） in renal of diabetes rats at early stage. And to discuss the relationship between PKC, VEGF and their effects on diabetie nephropathy（DN）. [Methods] Male SD rats were induced to diabetic rats model with streptozotoein. Rats were divided into control group and two, four -week diabetic rats group. Cut off the head and separate the glomendi, then pick up membrane protein and cytosolic protein. The PKC activity in renal glomerular of each rat was determined by radioimmunoassay. The change of VEGF expression in renal tissue of each rat was obversed by immunohistoehemistry. Meantime, blood glucose, kidney weight, body weight, urine ereafinine and serum creatinine were measured. And the ratio of kidney weight and body weight, ereatinine clearanee（Ccr） were counted. [Results] Membrane PKC activity of glomeruli were signitieantly elevated in two, four-week diabetic rats than control rats（P 〈0.05）. And there were not significant differences in the eytosolic PKC concentration of glomeruli among three groups （P 〉0.05）. And membrane PKC activity has positive relationship with ratio of kidney/body weight and Ccr（P 〈0.01）. The expression of VEGF in the renal tissue were significantly elevated in two, four-week diabetic rats than that of control rats. PKC activity had positive relationship with VEGF expression in renal tissue, and they had positive relationship with pathologic change in kidney. [Conclusion] Continued hyperglyeemia may lead to the PKC activity, and the PKC activity may lead to the expression of VEGF. They have important effect on the happeness and develooment of DN.

关 键 词：蛋白激酶C 糖尿病肾病 血管内皮细胞生长因子 

分 类 号：R587.1[医药卫生—内分泌]