蛋白激酶C和TGF-β1在糖尿病大鼠肾脏中的表达  

Expression of protein kinase C and transforming growth factor β1 in kidney of diabetic rats

作　　者：徐静[1] 李忠诚 易兰兰[1] 王俊宏[1] 张春虹[1] 戴信刚[1] 杨新利[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 [2]陕西省乾县人民医院

出　　处：《中国老年学杂志》2006年第3期343-345,共3页Chinese Journal of Gerontology

基　　金：陕西省自然科学基金资助项目(2003C234)

摘　　要：目的研究糖尿病大鼠肾小球中蛋白激酶C(PKC)活性变化和转化生长因子-β1(TGF-β1)的动态变化,探讨二者之间相互关系及其与糖尿病肾病(DN)发生发展的关系。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 w组(DM2)和糖尿病4 w组(DM4)。断头处死,分离肾小球,提取纯化胞浆及胞膜蛋白,利用〔γ3-2P〕-ATP底物磷酸化的方法检测胞浆及胞膜PKC活性。用免疫组织化学和400倍光镜检测TGF-β1在各组大鼠肾脏的表达。结果(1)糖尿病大鼠肾小球细胞内总的PKC活性与对照组无显著性差异,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。(2)糖尿病组TGF-β1的表达多于正常组。(3)肾小球细胞膜PKC活性与TGF-β1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TGF-β1的表达,在糖尿病早期肾内血流动力学改变中发挥着重要的调控作用。Objective To study the dynamic changes in protein kinase C （PKC） and transforming growth factorβ1 （TGF-β1） in renal of diabetic rats and to explore the relationship between PKC and TGF-β1 and their relation to diabetic nephropathy （DN）. Methods The rats were randomly divided into normal control group, diabetic 2 weeks （DM2） group, and diabetic 4 weeks （DM4） group （diabetic model induced by streptozotocin）. The rats were killed to separate glomeruli to extract purified cellular plasma and membrane protein to determine PKC activity by （γ-32P）-ATP substrate phosphorlation. TGF-β1 expression in kidney were determined by immunohistochemical assay and optical microscope. Results ①There were no significant differences in total PKC activity in glomeruli between diabetic rats and controls, PKC activity in cellular plasma slightly decreased. PKC activity in cellular membrane in diabetic rats were significandy higher than that of controls, the membrane PKC binding rate obviously increased, positively related to kidney hypertrophy index and creatinine clearance （Ccr）. ②TGF-β1 expression in diabetic group were higher than that of controls. ③PKC activity in cellular membrane positively related to TGF-β1 expression. Conclusions Continued high glucose could induce increased PKC activity in glomeruli and TGF-β1 expression, which play imoortant regulative role in hemodvnamic change of early DN.

关 键 词：蛋白激酶C 糖尿病肾病 转化生长因子-Β1 

分 类 号：R587.1[医药卫生—内分泌]