摘要
目的观察替米沙坦对单侧输尿管梗阻(UUO)模型大鼠肾间质纤维化(RIF)的影响,并探讨其可能机制。方法将24只大鼠随机分为假手术组(给予假手术)、模型组和替米沙坦组(采用UUO法制备大鼠RIF模型)各8只。手术前2d开始,替米沙坦组给予替米沙坦10mg·kg-1.d-1。术后2周处死大鼠,测定血清尿素氮(BUN)、血肌酐(Scr),光镜观察肾间质病理改变,免疫组织化学法检测肾组织α-平滑肌肌动蛋白(α-SMA)和纤维连接蛋白(FN)。结果模型组与替米沙坦组大鼠血清Scr、BUN上升,与假手术组比较均差异有显著性(均P<0.05);模型组、替米沙坦组RIF程度均较假手术组明显增高(均P<0.05);模型组α-SMA、FN的表达增加,与假手术组比较均差异有极显著性(均P<0.01);替米沙坦组与模型组比较,α-SMA、FN的表达下降,均差异有显著性(均P<0.05)。结论α-SMA和FN在UUO模型RIF过程中在肾组织中表达显著增高;替米沙坦能降低UUO大鼠BUN、Scr水平,改善肾功能,抑制UUO大鼠肾组织α-SMA和FN表达上调,减少UUO大鼠RIF面积。
Objective To investigate the effects of Telmisartan on renal fibrosis in rats caused by unilateral urethral obstruction (UUO) and its mechanism.Methods Adult male SD rats (n=24) were randomly divided into three groups:Sham-operated group for control(Sham),UUO group,Telmisartan group(treated with Telmisartan at 10 mg·kg-1·d-1 2 d before operation).Rats were sacrificed 2 weeks after operation.BUN and Scr in sura were measured.The renal interstitial fibrosis was observed under light microscopy with Masson and HE staining,and the expression of α-SMA and FN were detected by immunohistochemistry.Results The levels of BUN,and Scr,and the degree of renal interstitial fibrosis in UUO group and Telmisartan group were significantly higher than those in Sham group.The expression of a-SMA and FN in UUO group significantly increased in comparison to those in the sham operation group(P〈0.01).Compared with the UUO group,the Telmisartan group had significantly decreased expression of a-SMA and FN (P〈0.05).Conclusion The renal α-SMA and FN are highly expressed in the process of renal interstitial fibrosis.Telmisartan inhibits the renal interstitial fibrosis lesion,decreases BUN and Scr levels and down-regulates the expression of α-SMA and FN in UUO rats.
出处
《医药导报》
CAS
2010年第11期1422-1425,共4页
Herald of Medicine