多肽调控因子AcSDKP对单侧输尿管梗阻大鼠肾间质纤维化的抑制作用

目的:观察N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)对单侧输尿管梗阻(UUO)所致大鼠肾间质纤维化的抑制作用并初探其机制。方法:将18只大鼠随机均分为假手术组(生理盐水)、模型组(生理盐水)、治疗组(400μg·kg-1AcSD-KP),皮下注射给药1d(每天2次)后,后2组建立UUO模型,各组给药至造模后第14天处死大鼠,观察各组肾组织病理改变,检测肾组织转化生长因子β(1TGF-β1)、血管内皮生长因子(VEGF)蛋白及二者mRNA的表达。结果:与假手术组比较,模型组和治疗组大鼠肾小管变性及肾间质纤维化程度严重(P<0.05),TGF-β1及其mRNA表达水平明显增强(P<0.05),VEGF蛋白及其mRNA表达水平明显减弱(P<0.05);与模型组比较,治疗组大鼠肾小管变性及肾间质纤维化程度明显改善(P<0.05),TGF-β1及其mRNA表达水平明显减弱(P<0.05),VEGF蛋白及其mRNA表达水平明显增强(P<0.05)。结论:AcSDKP可能通过减弱TGF-β1、增强VEGF的表达以达到抑制肾间质纤维化的作用。

Inhibition Effect of AcSDKP on Unilateral Ureteral Obstruction-induced Renal Interstitial Fibrosis in Rats

OBJECTIVE： To investigate the inhibition effect of Acetyl-Ser-Asp-Lys-Pro （AcSDKP） on unilateral ureteral obstruction （UUO）-induced renal interstitial fibrosis in rats and its mechanism. METHODS： 18 male rats were randomly divided into sham-operated group （normal saline）, model group （normal saline） and treatment group （400 ？g·kg-1 AcSDKP）. Those rats were given hypodermic injection twice a day for 1 day to establish UUO models. Rats were sacrificed 14 days later. Histological change of renal tissue was observed. The protein expression and mRNA expression of transforming growth factor β1 （TGF-β1） and vascular endothelial growth factor （VEGF） in renal tissues were detected. RESULTS： Compared with sham-operated group, model group and treatment group exhibited severe renal interstitial fibrosis and the level of TGF-β1 and its mRNA expression were enhanced （P0.05）, while the protein and mRNA expression of VEGF were attenuated （P0.05）. Compared with model group, tubular degeneration and renal interstitial fibrosis were improved （P0.05） and the level of TGF-β1 and its mRNA expression were attenuated （P0.05）; the protein expression and mRNA expression of VEGF were enhanced significantly （P0.05） in treatment group. CONCLUSION： AcSDKP might attenuate the expression of TGF-β1 and enhance the expression of VEGF to inhibit renal interstitial fibrosis.