目的 观察色素上皮衍生因子(PEDF)、血小板反应蛋白-1(TSP-1)在糖尿病大鼠肾脏的表达变化,探讨促血管生成素-1(Ang-1)对上述因子的影响. 方法 将雄性SD大鼠分正常对照(NC)组、DN组、空载处理(BV)组、Ang-1处理(AV)组.采用STZ腹腔注射诱导大鼠DN模型.成模8周后尾静脉注射Ang-1腺病毒载体.多时点检测24 hUAlb和肾组织PEDF、TSP-1蛋白及mRNA表达水平.结果 DN、BV、AV组24 hUAlb均升高,其中AV组于20周后降低(P<0.05).DN、BV、AV组肾组织PEDF蛋白及mRNA表达下调,TSP-1表达上调(P<0.05),其中AV组12周后肾组织PEDF和TSP-1mRNA及蛋白表达变化较DN、BV组改善明显(P<0.05). 结论 糖尿病大鼠肾脏PEDF、TSP-1异常表达参与DN发生发展,给予Ang-1可改善糖尿病大鼠肾脏PEDF、TSP-1异常表达.
Objective To observe the expressions of thrombospondin-1 (TSP-1) and pigment epithelium-derived factor (PEDF),and investigate the effect of recombinant adenovirus angiopoietin-1 (Ang-1) on these factors in renal tissue of diabetic rats.Methods Rat model of diabetic nephropathy was induced by a single intraperitioneal injection of STZ.The subjects were divided into four groups:control (NC) group,DN group,blank vector (BV) group and Ang-1 treated (AV) group.The urinary protein were observed at 8th,12th,20th and 28th week.The expression levels of protein and mRNA of PEDF,TSP-1 in renal tissue at the same time points were detected by immunohistochemistry and real-time PCR.Results 24 hUAlb in DN,BV and AV groups were higher than those in NC group,but increased 24 hUAlb in AV group was decreased after 20th weeks (P〈0.05).Immunostaining score and PEDF mRNA level in DN,BV and AV groups were decreased,and TSP-1 were increased as compared with NC group (P〈0.05).In AV group,decreased protein and mRNA levels of PEDF were upregulated,and increased TSP-1 were downregulated after 12th weeks,as compared with DN or BV groups (P〈0.05).Conclusion The abnormal expression of TSP-1 and PEDF may play a role in the development of DN.Ang-1 administration can improve abnormal levels PEDF and TSP-1 in kidney of diabetic rat.