氯沙坦对进展性肾炎模型大鼠肾小管-间质细胞低氧诱导因子及结缔组织生长因子的影响研究  

Effects of Losartan on Tubulointerstitial Hypoxia Inducible Factors and Connective Tissue Growth Factors in Progressive Nephritis Model Rats

作　　者：查艳[1] 何平红[1] 龙艳君[1] 袁静[1] 俞雷 

机构地区：[1]贵州省人民医院肾内科,贵阳市550004 [2]贵州省电力医院,贵阳市550004

出　　处：《中国药房》2011年第29期2711-2713,共3页China Pharmacy

基　　金：贵州省优秀科技教育人才省长专项资金项目(黔省专合字(2010)89号);贵州省"十一五"社会发展科技项目(黔科合SY字[2008]3058)

摘　　要：目的:探讨氯沙坦对进展性肾炎模型大鼠肾小管-间质细胞低氧诱导因子-1α(HIF-1α)和结缔组织生长因子(CTGF)的影响及其肾保护作用机制。方法:将大鼠行右肾切除并注射鼠单克隆IgG(OX-7)抗Thy1.1抗体2次建立进展性肾炎大鼠模型,建模成功后取部分大鼠作为模型组,将剩余大鼠再分为对照组和氯沙坦高、低剂量组(80、20mg·kg-1·d-1);另取大鼠设立假手术组,每组5只,各组灌胃给予相应药物连续4周,观察各组大鼠24h尿蛋白、血肌酐、HIF-1α mRNA、CTGF mRNA水平及肾组织病理变化。结果:与假手术组比较,模型组血肌酐、24h尿蛋白和肾间质面积、HIF-1αmRNA、CTGF mRNA表达均明显增强(P<0.01或P<0.001);与模型组比较,氯沙坦高、低剂量组血肌酐、CTGF mRNA表达均明显降低(P<0.05或P<0.01),但在24h尿蛋白、肾间质面积比值、HIF-1αmRNA水平方面氯沙坦高剂量组均明显降低(P<0.01),低剂量组无明显变化。病理观察发现,模型组大鼠肾小管-间质炎症细胞浸润并出现纤维化,氯沙坦高、低剂量组肾小管-间质的损伤较对照组均有改善。结论:氯沙坦可能通过降低进展性肾炎模型大鼠HIF-1α mRNA和CTGF mRNA表达,减轻肾小管-间质纤维化而发挥肾脏保护作用。OBJECTIVE： To probe into the effects and mechanism of losartan on tubulointerstitial hypoxia inducible factor-1 （HIF-1α） and connective tissue growth factor （CTGF）in progressive nephritis model rats. METHODS： The rats underwent right ne- phrectomy and was injected with IgG（OX-7） mouse monoclonal anti-Thyl. 1 antibody twice to establish progressive nephritis model. Then some model rats were included in model group and other rats were divided into control group and losartan high-dose and low-dose groups （80, 20 mg.kg-1.d-1）, some rats were selected and included in sham operation group with 5 rats in each group. Above three groups were given relevant drugs for four weeks intragastricaUy. The levels of 24 h urine protein, serum creatinine, HIF-1α mRNA and CTGF mRNA and pathological changes of kidney were observed. RESULTS： Compared with sham operation group, serum creatinine, 24 h urine protein, renal interstitium area, HIF-1α mRNA and CTGF mRNA expression in model groups increased significantly （P（0.01 or P（0.001） ; compared with model group, serum creatinine and CTGF mRNA expression in losartan high-dose and low-dose groups decreased significantly （P（0.05 or P（0.01）, while 24 h urine protein, renal interstitium area and HIF-1α mRNA level in losartan high-dose group decreased significantly （P（0.01） and had no obvious change in losartan low-dose group. Pathological observation of model group showed that inflammatory cell infiltration and renal fibrosis. Tubulointerstitial injury was ameliorated in losartan high-dose and low-dose groups, compared with control group. CONCLUSIONS： Losartan may protect kidney by decreasing the expression of HIF-1α mRNA and CTGF mRNA and tubulointerstitial fibrosis in the progres- sive nenhritis model rats.

关 键 词：氯沙坦 进展性肾炎 大鼠 低氧诱导因子-1 α 结缔组织生长因子 

分 类 号：R965[医药卫生—药理学] R972.4[医药卫生—药学]