二酯酰甘油-蛋白激酶C信号传导系统和细胞因子与糖尿病肾病的关系  

The relationship between DAG-PKC signal conducting system and cellular factor and diabetic nephropathy

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

出　　处：《西安交通大学学报（医学版）》2006年第2期168-172,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

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)的活性变化及转化生长因子-β1(TGF-β1)和血管内皮细胞生长因子(VEGF)的表达情况,探讨3者之间的相互关系及其与糖尿病肾病(DN)发生、发展的相关性。方法选用雄性SD大鼠,用链脲佐菌素制备大鼠糖尿病实验模型,随机分为正常对照组、糖尿病2周(DM2)组和糖尿病4周(DM4)组。大鼠断头处死,分离肾小球,提取纯化胞浆及胞膜蛋白。利用[r-32P]-ATP底物磷酸化的方法检测胞浆及胞膜PKC活性;用免疫组织化学法检测VEGF和TGF-β1在各组大鼠肾小球及肾小管中的表达。结果①DM2、DM4组肾小球细胞内总的PKC活性与对照组无显著性差异,胞浆PKC活性略有下降,但相差不显著(P>0.05);DM2、DM4组肾小球细胞膜PKC活性均明显高于正常对照组(P<0.05),且细胞膜PKC活性与肾脏肥大指数(肾重/体质量)和内生肌酐清除率(Ccr)呈正相关。②DM2、DM4组VEGF和TGF-β1的表达均高于正常对照组(P<0.01)。③肾小球细胞膜PKC活性与VEGF和TGF-β1的表达呈正相关。结论高血糖慢性刺激可引起肾小球PKC活性增高,并上调TGF-β1和VEGF的表达,进一步导致肾小球滤过膜通透性和滤过率增加,这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 explore the activation of protein kinase C（PKC） and the expression of transforming growth factor β1 （TGF-β1） and vascular endothelial growth factor（VEGF） in renal of diabetic rats at early stage, and to discuss the relationship of PKC, TGF-β1 and VEGF and their effects on diabetic nephropathy （DN）. Methods Male SD rats were induced to diabetic rat model with streptozotocin. Rats were randomly divided into control group and two, four-week diabetic group. After all group rats were killed, glomeruli were separated and membrane protein and cytosolic protein were picked up. The activity of PKC in renal glomeruli of each rat was detected by radioimmunoassay. The change of TGF-β1 and VEGF expression in renal tissue of each rat was observed by immunohistochemistry. Results ① Membrane PKC activity of glomeruli were significantly elevated in two, four-week diabetic rats than that in control group（P〈0.05）. There were no significant differences in＇the cytosolic PKC concentration of glomeruli among three groups （P〉0.05）. Membrane PKC activity had positive relationship with raito of kidney/body weight and Ccr（P〈0.01）. ② The expression of TGF-β1 and VEGF in the renal tissue were significantly elevated in two, four-week diabetic rats than that of control. ③ The activation of membrane PKC had positive relationship with expression of TGF-β1 and VEGF. Conclusion Hyperglycemia may lead to the activation of PKC, and the activation of PKC may lead to the expression of TGF-β1 and VEGF. They take important effect on the occurrence and development of DN.

关 键 词：蛋白激酶C 糖尿病肾病 转化生长因子-Β1 血管内皮生长因子 

分 类 号：R587.1[医药卫生—内分泌]