Objective To investigate the effect of losartan,an angiotensin 1I type 1 receptor antagonist(ATlRA),on transforming growth factor-β1 expression in alcoholic nephropathy in rats.Methods Male adult Wistar rats were random divided into three subgroups and treated daily for 12 weeks as follows,rats were treated with normal saline[20ml/(kg·d)gavage twicely]in vehicle group,rats were treatedwith alcohol[400g/L,8g/(kg·d)gavage twieely]in alcoholic nephropathy,and rats were concomitantly treated with alcohol and Iosartan [200mg/L,ling/(kg·d),gavage]in alcohol+losartan.HE staining,Sirius red staining,electronic microscope,and immunohistochemistry were used to examine histologic changes,collagen fibers deposition,and the expression of TGF-BI.Results Compared with vehicle treated rats,alcoholic nephropathy rats showed tubular vacuolation,granular degeneration,swelling,tubulointerstitial inflammatory cell infil tration,and rarely mesangial proliferation and matrix deposition.Sirius red staining displayed a significant increase in collagen fibers in alias of glomemli,tubulointerstitium and vessels.Concomitant administration of losartan reversed all of above parameters(P<0.05).The upregulated expression of TGF-β1 proteins was significantly suppressed by losartan treatment(P<0.05).Conclusions These findings suggest that alcoholic nephropathy is characterized by the tubular granular degeneration,vacuolation,swelling,and tubulointemtitial inflammato-ry cell infiltration,and this is associated with upregulation of TGF-β1.Losartan treatment offers protection effect by downregulating TGF-β1 expression.%目的 研究血管紧张素Ⅱ1型受体拮抗荆(AT1RA)洛沙坦对酒精性肾损伤大鼠肾脏转化生长因子-β1(TGF-β1)表达的影响.方法 雄性成年Wistar大鼠随机分3组:对照组以生理盐水20 ml/(kg·d)灌胃2次/d;酒精性肾损伤组以400 g/L酒精8g/(kg·d)灌胃2次/d;治疗组以等量酒精灌胃基础上以洛沙坦1 mg/(kg·d)灌胃1次/d.12周后,以苏木素-伊红染色(HE)和透射电镜观察各组肾脏病理变化,天狼星红(Sirius red)苦味酸染色观察胶原纤维,免疫组化法检测TGF-β1在肾脏中的表达.结果 与对照组相比,酒精性肾损伤大鼠肾小球系膜细胞及系膜基质轻度增殖,肾小管可见颗粒变性、空泡变性、肿胀,问质内炎性细胞浸润,肾小球、间质及血管周围胶原纤维沉积显著增加,TGF-β1在肾小球及血管周围肾小管上皮细胞内的表达明显增加(P<0.05);洛沙坦治疗组上述病变均减轻,特别是TGF-β1蛋白的表达显著下降(P<0.05).结论 酒精性肾损伤以小管颗粒变性、空泡变性、肿胀,间质内炎性细胞浸润为特征.这些改变与TGF-β1在肾小管问质内的表达增加有关.而洛沙坦可下调TGF-β1的表达,从而发挥其肾保护效应.
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