【摘要】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(NCG)组、糖尿病肾病(DNG)组、空载处理(BVG)组、Ang-1处理(AVG)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UAlb/Cr和肾组织PEDF、TSP-1 蛋白及mRNA表达水平。 结果　DNG、BVG、AVG组UAlb/Cr均升高，其中AVG组于20周后降低(P<0.05)。DNG、BVG、AVG组肾组织PEDF蛋白及mRNA表达下调，TSP-1表达上调(P<0.05)，其中AVG组12周后肾组织PEDF和TSP-1 mRNA及蛋白表达变化较DNG、BVG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。

　　【关键词】糖尿病肾病;促血管生成素1;血小板反应蛋白1;色素上皮衍生因子

　　【Abstract】Objective To observe the expressional changes 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 streptozotocin. The subjects were divided into four groups: control (NVG) group, diabetic (DNG) group, blank vector (BVG) group and Ang-1 treated (AVG) group. The urinary protein were observed at 8th, 12th, 20th and 28th week. The expressional levels of PEDF, TSP-1 protein and mRNA in renal tissue at the same time points were detected by immunohistochemistry and real-time PCR. Results UAlb/Cr in DNG, BVG and AVG groups were higher than that in NVG group, but increased UAlb/Cr in AVG group was decreased after 20th weeks (P<0.05). Immunostaining score and PEDF mRNA level in DNG, BVG and AVG groups were decreased, and TSP-1 were increased as compared with NVG group (P<0.05). In AVG group, decreased protein and mRNA levels of PEDF were upregulated, and increased TSP-1 were downregulated after 12th weeks, as compared with diabetic or blank vector groups (P<0.05). Conclusion The abnormal expression of TSP-1 and PEDF may play a part in the development of DN. Ang-1 administration can improve abnormal levels PEDF and TSP-1 in kidney of diabetic rat.

　　【Key words】Diabetic nephropathy (DN);Angiopoietin-1 (Ang-1);Thrombospondin-1 (TSP-1);Pigment epithelium-derived factor (PEDF)