洋川芎内酯A 对单侧输尿管梗阻大鼠肾间质纤维化的作用及机制研究

目的:探讨洋川芎内酯A(SenA)对单侧输尿管梗阻(UUO)大鼠肾脏病变的保护作用。方法:50只雄性SD大鼠随机分为假手术组、模型组、SenA低剂量(20 mg/kg)组、SenA高剂量(40 mg/kg)组及阳性对照(厄贝沙坦,20 mg/kg)组,行UUO术制备单侧输尿管模型,并于术后21天处死大鼠。根据试剂盒说明书检测血清尿素氮(BUN)、肌酐(Scr)的含量,HE染色法观察肾脏病理改变,免疫组化法检测肾组织α-SMA及CollagenⅠ蛋白的表达,Western blotting检测各组大鼠肾皮质Wnt4、β-catenin、p-GSK-3β、E-cadherin的表达水平。结果:与模型组比较,SenA低、高剂量组及阳性对照组大鼠血清中Scr、BUN含量明显降低(P<0.05),肾脏病变情况得到不同程度的改善。同时,SenA可明显减少大鼠肾组织中α-SMA和CollagenⅠ蛋白的分泌(P<0.05),下调Wnt4、β-catenin及p-GSK-3β的表达水平(P<0.05),并伴有E-cadherin蛋白表达显著上调(P<0.01)。结论:SenA可通过下调Wnt4/β-catenin信号通路,抑制肾组织细胞外基质沉积并改善肾功能,最终改善UUO模型大鼠肾间质纤维化的病变进程。

Effect and Mechanism of Senkyunolide A on Renal Interstitial Fibrosis in Unilateral Ureteral Obstruction

Objective To study the renal protective effect of Senkyunolide A(SenA)in rats with unilateral ureteral obstruction(UUO).Methods 50 male SD rats were randomly divided into the sham operation group,the model group,the Sen A low dose(20 mg/kg)group,the SenA high dose(40 mg/kg)group and the positive control group(Irbesartan,20 mg/kg).The unilateral ureter model was prepared by UUO and the rats were killed on the 21th day after operation.According to the kit instruction,the serum content of Scr and BUN were detected.HE staining was used observing the renal pathological changes.Immunohistochemical method was used detecting kidney tissues ofα-SMA protein expression.Western blotting analysis was used measuring Wnt4,β-catenin,p-GSK-3βand E-cadherin expression level.Results Whencompared with the model group,theserum contents of Scr and BUN in each treatment group were significantly reduced(P<0.05),and the kidney damage was improved to different degrees.At the same time,the SenAcouldobviously reduce theα-SMA in rat kidney(P<0.05),down-regulated the Wnt4,β-catenin and p-GSK-3βexpression levels(P<0.05),accompanied with E-cadherin protein expression significantly up-regulated(P<0.01).Conclusion Senkyunolide A can downregulate Wnt4/β-catenin signaling pathway,inhibit extracellular matrix deposition in renal tissue,improve renal function,and ultimately reverse the process of renal interstitial fibrosis in UUO rats.