›› 2005, Vol. 4 ›› Issue (11): 618-621.

• 论著 • 上一篇    下一篇

氯沙坦对梗阻性肾病大鼠肾间质固有细胞的作用

刘欣颖1 毛佩菊1 顾 勇2 林善琰2   

  1. 200336 1. 上海,上海市长宁区中心医院肾脏内科 2. 上海,复旦大学附属华山医院肾内科
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2005-11-12 发布日期:2005-11-12

  • Received:1900-01-01 Revised:1900-01-01 Online:2005-11-12 Published:2005-11-12

摘要: 目的 研究氯沙坦对梗阻性肾病大鼠肾间质固有细胞的作用,寻找可能的临床抑制肾间质纤维化的方法。方法 采用单侧输尿管结扎(UUO)模型,治疗组于造模当日至造模后14天给予科素亚(16 mg/kg/d)灌胃,另设假手术组及手术组作为对照。应用免疫组织化学方法检测肾间质TGF-β的表达,组化双染色观察α-SMA、E-钙粘素的表达。激光共聚焦显微镜观察间质小管区α-SMA表达。 结果 手术组两周时出现近端肾小管区TGF-β表达明显增高(P<0.01),伴α-SMA表达增高(P<0.01),E-钙粘素表达下降(P<0.05),部分肾小管细胞中可见α-SMA及E-钙粘素同时表达;治疗组与手术组相比TGF-β、α-SMA的表达明显下降(P<0.05),而E-钙粘素的表达上调(P<0.05)。共聚焦显微镜下见部分小管基底膜损伤,上皮细胞表达α-SMA。结论 氯沙坦可通过抑制肾间质固有细胞转分化过程的进展,从而对肾间质纤维化具有治疗作用。

关键词: 氯沙坦, 肾间质纤维化, 转分化

Abstract: Objective To investigate the effect of ATRA Losartan on rats renal interstitial cells after unilateral ureteral obstraution(UUO). Methods The UUO models were induced by ligating the right ureter.Rats were divided into normal control(sham operation), model and treatment group(Losartan 16 mg/kg/d by gastric gavage from the same operation day to day 14 after the induction of UUO). The expression of TGF-β was detected by immunohistochemical staining. E-cadherin and α-SMA was analyzed by double-labeled immuno-histochemical staining. And FITC-labledα-SMA was also observed by confocal laser scanning microscopy. Results The obstructed kidney displayed interstitial fibrotic lesions at 14 days after UUO. The TGF-βwas overexpressed(P<0.01), with upregulated α-SMA(P<0.01), and decrased E-cadherin level(P<0.05). Both E -cadherin and α-SMA’s were expression seen in many tubular epithelium cells. And tubular basement membrane lesion was seen in confocal microscopy. Compared with the UUO group, losartan treatment largely blunted the expression of TGF-β and α-SMA(P<0.01), the level of E-cadherin was upregulated. Conclusion Losartan could significantly suppress the progression of transdifferentiation of interstitial resident cells, and therefore exhibits potent therapeutic effects on renal interstitial fibrosis.

Key words: Renal interstitial fibrosis, Transdifferentiation

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