血管紧张素受体拮抗剂在进展性肾炎大鼠模型中对慢性低氧引起肾小管间质损害的抑制作用(1)
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[摘要] 目的:观察并探讨血管紧张素受体拮抗剂(ARB,氯沙坦)对进展性肾炎大鼠肾小管间质低氧诱导因子-1α(HIF-1α)的影响及肾小管间质损害的抑制作用。方法:将大鼠随机分为假手术组、模型组和不同剂量氯沙坦治疗组,除假手术组外,其余各组行右肾切除并两次注射IgG(OX-7)mouse monoclonal anti-Thy1.1 antibody 建立进展性肾炎大鼠模型,各组分别予饮用水或不同剂量氯沙坦灌胃4周,观察各组大鼠肾功能、尿蛋白、收缩压、HIF-1α表达及肾组织病理的改变。结果:与模型组比较,氯沙坦组大鼠尿蛋白减少,肾功能改善,肾小管间质HIF-1α mRNA含量显著减少,肾组织病理改变明显减轻,尤其在大剂量氯沙坦组。结论:氯沙坦抑制了进展性肾炎大鼠肾小管间质的损害可能与改变HIF-1α的表达有关。
[关键词] 血管紧张素受体拮抗剂;慢性低氧;进展性肾炎;低氧诱导因子-1α
[中图分类号] R-332 [文献标识码]A[文章编号]1674-4721(2011)08(a)-015-04
Chronic hypoxia inducing tubulointerstitial injury is inhibited by Angiotensin II receptor blocker in a progressive model of rat glomerulonephritis
ZHA Yan1, YU Fangfang1, SHEN Yan1, ZHA Yong2*
1.Department of Nephrology, Guizhou Province People′s Hospital, Guizhou Province, Guiyang 550004, China; 2. Guizhou Province Department of Public Health, Guizhou Province, Guiyang550004, China
[Abstract] Objective: To observe and probe into the effects of angiotensin Ⅱ receptor blocker (ARB, losertan) on hypoxia inducible factor-1α (HIF-1α) and the inhibition of tubulointerstitial injury in a progressive model of rat glomerulonephritis. Methods: The rats were randomly divided into sham operation, model and different doses losartan therapy groups. Excepted the sham operation group, the rest groups underwent right nephrectomy and injected IgG (OX-7) mouse monoclonal anti-Thy1.1 antibody twice, were established as progressive nephritis model. Either drink water or different doses losartan were irrigated into the stomachs of the rats in all groups for 4 weeks. And the effects of losartan on renal function, proteinuria, SBP, HIF-1α mRNA, and the tubulointerstitial pathological changes were examined. Results: In losartan therapy groups, proteinuria was decreased, the renal function was improved, and these expression of HIF-1α mRNA was suppressed. Tubulointers titial injury was ameliorated. Regression of histological damage was observed in losartan therapy groups, especially in high dose losartan group ......
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