慢性低氧对进展性肾炎大鼠肾小管间质损害.doc

慢性低氧对进展性肾炎大鼠肾小管间质损害[摘要] 目的：观察并探讨慢性低氧对进展性肾炎大鼠小管间质低氧诱导因子-1α（HIF-1α）的影响及肾小管间质的损害。方法：将大鼠随机分为假手术组、4周和8周模型组。除假手术组外，模型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，观察各组大鼠肾功能、尿蛋白、收缩压、HIF-1α表达及肾小管间质的病理改变。 结果：与假手术组比较，4周和8周模型组大鼠尿蛋白进行性增加，肾功能减退，肾小管间质HIF-1amRNA含量显著增加，肾组织病理改变明显加重，尤其在8周模型组。结论：慢性低氧可能通过引起HIF-1α的高表达而导致进展性肾炎大鼠小管间质的损害。 [关键词] 慢性低氧；进展性肾炎；低氧诱导因子-1α；大鼠 [中图分类号] R692.3 [文献标识码]A [文章编号]1674-4721（2011）07（b）-０14－０3 Chronic hypoxia induces tubulointerstitial injury in a progressive model of rat glomerulonephritis ZHA Yan1, HU Ying1, HUANG Douquan1, HUANG Zhaohui1, ZHA Yong2* 1.Guizhou Province People Hospital, Guizhou Province, Guiyang 550004, China; 2.Guizhou Province Department of Public Health, Guizhou Province, Guiyang 550004, China [Abstract] Objective: To observe and probe into the effects of hypoxia inducible factor-1α(HIF-1α) and tubulointerstitial injury in a progressive model of rat glomerulonephritis. Methods: The rats were randomly divided into sham operation, 4 weeks and 8 weeks model groups. Except 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. Renal function, proteinuria, SBP, HIF-1α mRNA and the tubulointerstitial pathological changes were examined. Results: Compared with the sham operation group, proteinuria was increased, the renal function was decreased, and these expression of HIF-1α was strong. Tubulointerstitial injury was observed, especially in 8 weeks model group. Conclusion: Chronic hypoxia may induce tubulointerstitial injury by increasing the expression of HIF-1α in the progressive model of rat glomerulonephritis. [Key words] Chronic hypoxia; Progressive nephritis; Hypoxia inducible factor-1α; Rat 近来Fine LG等[1]提出肾小管-间质细胞的慢性低氧可能在肾纤维化的发生、发展中起重要作用。因此我们在进展性肾炎（progressive nephritis）大鼠模型[2]中，以氧浓度敏感的低氧诱导因子-1α(Hypoxia inducible factor-1α,HIF-1α)为低氧标志物，观察在慢性低氧状态下，肾小管间质细胞HIF-1α的表