磷酸化的cAMP反应元件结合蛋白_1在糖尿病大鼠肾小球中表达增强

Increased expression of phosphorylating-cAMP-responsive element binding protein_1 in early diabetic glomeruli

目的探讨磷酸化的cAMP反应元件结合蛋白1(P CREB1)在糖尿病大鼠肾组织中的表达特征及与细胞外基质积聚的关系。方法雄性Wistar大鼠切除右肾2周后随机分为对照组和糖尿病组,用链脲佐菌素复制糖尿病模型。分别于1、2、4、8和12周用免疫组化检测纤维黏连蛋白(FN)、层黏连蛋白(LN)及P CREB1的表达,Western印迹和RT PCR检测肾皮质CREB1磷酸化(活性)及mRNA的表达。结果糖尿病组FN与LN在4周时开始升高,并持续到12周。CREB1的活性及其mRNA在2、4和8周增高,在12周时降至正常。结论CREB1可能在糖尿病肾病细胞外基质积聚中发挥一定作用。

Objective To investigate the expression and significance of cAMP-responsive element binding protein 1 (CREB 1) in experimental diabetic nephropathy in rats over the course of 12 weeks. Methods Male Wistar rats were divided into two groups: Controland diabetic.Diabetic models were intraperitoneally given Streptozocin (STZ,65mg/kg).6 rats of each group were killed at 1,2,4,8 and 12 weeks. Immunohistochemistry and computer image-pattern analysis system were used to analyze the expression of FN, LN . The activation of CREB 1 was mesured by Western blot with the specific corresponding antibodies. CREB 1 mRNA was detected by RT-PCR. Results With the courses of diabetic nephropathy, expression of FN and LN was gradually higher. P-CREB 1 and mRNA in diabetic glomeruli was significantly increased in 2,4,8 weeks and then decrease in 12 weeks. Conclusion This activated CREB1 in diabetic glomeruli may,in part, play a role in the pathogenesis of extracellular matrix accumulation in diabetic nephropathy.