替米沙坦对4高盐饮食诱导肾脏纤维化的保护作用

摘要

Objective To study the improvement of telmisartan in renal fibrosis induced by 4% high-salt diet in Wistar rats.Meth-ods Thirty-six male Wistar rats were randomly divided into regular group with regular salt (0.5%),high salt group with high salt (4%) and high salt+Telmisartan group with high salt(4%)+telmisartan40 mg·kg-1·d-1. Tail artery pressure was determined at every 4 weeks. The 24 hours urine was collected by metabolic cages. The contents of microalbumin, creatinine of 24 hours were measured by biochemical methods. Pathological changes of renal cortex was observed by HE staining.The renal fibrosis was observed by Masson staining.In addition, the technique of western-blot was employed to determine the protein expression of α-smooth muscular actin(α-SMA),TGF-β1,p-Smad2/3,Smad7 in the renal cortex.Results Firstly,comparing with regular group,the blood pressure,fibrosis index of the glomerular, content of microalbumin and the urinary Na+ were increased in high salt group, creatinine clearance rate was decreased, protein expression of α-SMA,p-Smad2/3,Smad7 were much higher in high salt group as well. Secondly,after the intervention of telmisartan,the blood pressure,fi-brosis index of the glomerular and content of microalbumin were much lower than those of high salt group, all protein expressions were also significantly reduced (P<0.05).Conclusions TGF-β1/Smads signaling pathway might be involved in the development of renal fibrosis in-duced by long-term 4% high-salt diet in Wistar rats. Telmisartan might improve kidney damage via restraining TGF-β1/Smads signal path-way.%目的 探讨替米沙坦对4%高盐饮食诱导肾脏纤维化的保护作用.方法 雄性Wistar大鼠36只,随机分为普食组(0.5%正常盐);高盐组(4%高盐);高盐+替米沙坦组(4%高盐+替米沙坦40 mg·kg-1·d-1),每组12只.每4 w用鼠尾无创测压仪测量鼠尾动脉压;24 w末用代谢笼收集尿液,测定24 h尿微量白蛋白(MAU)、血尿肌酐(Cr)含量,苏木素-伊红(HE)染色观察肾皮质形态,Masson染色观察肾小球纤维化;Western印迹法检测皮质区α-平滑肌肌动蛋白(SMA)、转化生长因子(TGF)-β1、磷酸化Smad2/3(p-Smad2/3)、Smad7蛋白的表达.结果 与普食组相比,高盐组及高盐+替米沙坦组大鼠尾动脉收缩压显著升高(P<0.05),双肾重/体重、24 h尿MAU显著增高(均P<0.05),内生肌酐清除率(Ccr)显著降低(P<0.05);肾小球的纤维化指数明显增高(P<0.05);肾脏皮质区的TGF-β1、p-Smad2/3、Smad7蛋白表达显著增高(P<0.05).与高盐组比较,高盐+替米沙坦组大鼠尾动脉收缩压明显降低(P<0.05),24 h尿MAU显著下降(P<0.05),肾小球的纤维化指数明显降低(P<0.05),上述各蛋白表达也显著降低(均P<0.05).结论 长期4%高盐摄入可诱导Wistar大鼠TGF-β1/Smads信号通路表达增高导致肾脏纤维化;替米沙坦可能通过抑制TGF-β1/Smads信号通路减轻肾脏损伤.