阿托伐他汀对单侧输尿管梗阻大鼠肾间质纤维化的防治作用

Effects of atorvastatin on renal interstitial fibrosis of unilateral ureteral obstruction in rats.

目的观察阿托伐他汀对单侧输尿管梗阻(UUO)大鼠模型肾间质纤维化的作用及机制。方法采用单侧输尿管结扎术致肾间质纤维化大鼠模型,将大鼠随机分为3组:假手术组、UUO模型组、阿托伐他汀治疗组。手术后第1、4、7、10、14天处死大鼠,经HE染色、PAS染色、天狼星红染色,免疫组化、West-ern蛋白印迹分析方法,观察各组α-平滑肌肌动蛋白、Ⅰ型胶原、结缔组织生长因子、低密度脂蛋白受体相关蛋白及肾小管间质损伤指数。结果UUO模型组平滑肌肌动蛋白、Ⅰ型胶原、结缔组织生长因子、低密度脂蛋白受体相关蛋白的表达及肾小管损伤指数均明显高于假手术组(P<0.01),而阿托伐他汀治疗组明显低于模型组(P<0.01)。结论结缔组织生长因子、低密度脂蛋白受体相关蛋白与肾间质纤维化进展相一致;阿托伐他汀减少单侧输尿管梗阻侧大鼠肾脏低密度脂蛋白受体相关蛋白的表达,下调单侧输尿管梗阻侧大鼠肾脏Ⅰ型胶原、平滑肌肌动蛋白的表达,阿托伐他汀通过非降脂途径延缓UUO所致大鼠肾间质纤维化的程度。

Objective To investigate the effects of atorvastatin on renal interstitial fibrosis of unilateral ureteral obstruction （ UUO ） in rats and its mechanism. Methods The Rats model of renal interstitial fibrosis was made with unilateral urethral ligation, which were randomly divided into three groups： sham operation group （SOG） , model group （UUO）, atorvastatin treatment group. The rats were sacrificed at 1,4,7,10,and 14 day. Smooth muscle actin （a-SMAJ ,and collagen I, connective tissue growth factor（ CTGF）, low density lipoprotein receptor-related protein and renal tubule interstitial damage index were detected by HE staining, PAS staining, immunohistochemistry and Western blot respectively. Results The expression of CTGF,LRP,Collagen Ⅰ and a-SMA in UUO group was obviously higher than those in sham group （ P 〈 0.01 ） ,but significantly higher than those in atorvastatin treatment group （P 〈0.01 ）. Conclusion Connective tissue growth factor,low density lipoprotein receptor-related protein and renal interstitial fibrosis developed in the same way. Atorvastatin may decrease the expression of low density lipoprotein receptor-related protein,downregulate the expression of Collagen Ⅰ and a-smooth muscle actin and delay the development of renal interstitial fibrosis.