替米沙坦对UUO小鼠肾脏HIF-1α表达的影响及其与巨噬细胞的关系  

Effect of telmisartan on the expression of HIF-1α in mouse kidneys of unilateral ureter obstruction and its relationship to local macrophage infiltration.

作　　者：廖盼丽[1] 唐小铁[2] 曾锐[1] 裴广畅[1] 周璇[1] 常晓燕[1] 张颖[1] 刘晓城[1] 徐钢[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肾内科,武汉430030 [2]武汉科技大学附属普仁医院肾内科

出　　处：《中国组织化学与细胞化学杂志》2012年第3期218-223,共6页Chinese Journal of Histochemistry and Cytochemistry

基　　金：国家自然科学基金资助(30971372);国家青年科学基金资助(30800525)

摘　　要：目的研究单侧输尿管结扎小鼠肾脏缺氧诱导因子-1α(Hypoxia-inducible factor-1alpha,HIF-1α)的表达及替米沙坦对其表达的影响和机制。方法采用单侧输尿管结扎(UUO)建立肾间质纤维化小鼠模型。30只雄性CD1小鼠随机分为假手术组(0d)、单侧输尿管结扎7天组(7d)及14天组(14d)、单侧输尿管结扎7天及14天并替米沙坦(10mg.kg-1.d-1)治疗组(7dT、14dT)。MASSON染色观察肾脏病理改变;免疫组织化学检测各组α平滑肌动蛋白(α-SMA)、HIF-1α、巨噬细胞(F4/80)在肾脏组织中的表达及分布、连续切片检测HIF-1α与F4/80的共定位;Western-blot检测α-SMA、HIF-1α的变化。结果随时间进展,输尿管结扎小鼠(7d、14d)肾脏病理改变逐渐加重,α-SMA、HIF-1α、F4/80表达均增加,与假手术组相比有统计学意义(P<0.05);HIF-1α主要分布于肾间质细胞中,HIF-1α与F4/80存在明显的共定位现象;给予替米沙坦治疗后,它们的表达均下降(均P<0.05)。结论替米沙坦可抑制巨噬细胞的浸润,降低UUO小鼠HIF-1α的表达,减轻UUO小鼠肾脏纤维化。Objective To assess the effect of telmisartan on the expression of hypoxia induced factor 1 alpha HIF-lα in the kidneys of mice with unilateral ureter obstrucion. Methods Mouse renal interstitial fibrosis was produced by unilateral ureter obstruction （UUO）. Thirty male CD1 mice were randomly divided into the sham operation group（0d）, UUO model groups of 7 days（7d） and 14 days（14d）, UUO and telmisartan treatment （10mg · kg^-1 · d^-1）groups of 7 days（7dT） and 14 days（14dT）. Renal pathological changes were evaluated by MASSON staining. Immunohistochemistry was used to detect the distribution of α-SMA, HIF-lα, F4/80 and the colocalization of HIF-lα and F4/80 on serial sections. Western-blot was used to detect the protein expression of α-SMA and HIF-lα. Results The expression of α-SMA and HIF-lα in uuo mice（7d.14d） increased over time （P〈0.05）. HIF-lα and F4/80 were colocalizated in the renal interstitium. After treatment with telmisartan, they all decreased （P〈0.05）. Conclusion Telmisartan might inhibit the infiltration of macrophages, decrease the kidney expression of HIF-lα, and as a result, attenuate fibrosis in the kidney after unilateral ureter obstruction.

关 键 词：UUO 替米沙坦 缺氧诱导因子-1Α 巨噬细胞 

分 类 号：R322.61[医药卫生—人体解剖和组织胚胎学]