AngⅡ抑制剂对HIF-1α在慢性肾衰大鼠肾组织中表达的影响  

Effects of angiotensin Ⅱ inhibitor on HIF-1α expression in the renal tissue of 5/6th kidney ablation/infarction rats

作　　者：秦军燕[1] 王琛[1,2] 杨婧[1] 邵命海[1] 留寅清[1] 何立群[1,2] 

机构地区：[1]上海中医药大学附属曙光医院肾病科,上海200021 [2]上海市中医临床重点实验室,上海200021

出　　处：《第二军医大学学报》2012年第9期965-968,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30973723);上海市科委基金(08411962400);上海高校创新团队建设基金资助项目(201203)~~

摘　　要：目的观察AngⅡ抑制剂对于5/6(ablation/infarction,A/I)肾切除慢性肾衰大鼠残余肾组织HIF-1α蛋白及mRNA表达的影响,并初步探讨其作用机制。方法将SD雄性大鼠随机抽取15只设为假手术组(A组),其余采用5/6(A/I)肾切除慢性肾衰模型法制作成慢性肾功能衰竭动物模型,随机分为模型组(B组)和AngⅡ抑制剂(氯沙坦钾合福辛普利钠)组(C组),每组15只,分别给予相应干预,60 d后检测生化指标,并采用蛋白质印迹法和荧光定量PCR分别测定大鼠残余肾皮质、髓质HIF-1α蛋白及mRNA的表达。结果模型组与假手术组比较,SCr、BUN升高,CCr降低(P均<0.01);AngⅡ抑制剂组与模型组干预后比较,SCr、BUN水平下降,CCr水平升高(P均<0.05)。模型组大鼠肾皮质、髓质HIF-1α蛋白和mRNA的表达均较假手术组升高(P<0.05),AngⅡ抑制剂组HIF-1α蛋白和mRNA在肾皮质和髓质中的表达均较模型组减少(P<0.05)。结论 AngⅡ抑制剂可以改善5/6(A/I)肾切除慢性肾衰大鼠的肾功能,其作用机制可能与HIF-1α信号通路有关。Objective To investigate the influences of Angiotensin Ⅱ inhibitor on renal expression of HIF 1a mRNA and protein in the chronic renal failure （CRF） rats （induced by 5/6th kidney ablation/infarction [5/6A/I]） and the related mechanism. Methods SD rats were made into CRF model by means of 5/6th kidney ablation/infarction. The study was divided into sham operation group （Group A）, model group （Group B） and Angiotensin Ⅱ inhibitor（Cozaar-with Monopril） group （Group C）, each group containing 15 rats. The biochemical parameters of the rats were examined 60 days later in the 3 groups. The expression of HIF-1a mRNA and protein in the remnant renal cortex and medulla were assessed by Real-time PCR and Western blotting analysis. Results Compared with group A, group B had significantly increased SCr and BUN levels and significantly decreased CCr level（P〈0.01）. Compared with group B, group C had significantly decreased SCr and BUN levels and significantly increased CCr level（P〈0.05）. The expression of HIF-1a mRNA and protein in the renal cortex and medulla in group B was significantly higher than that in group A（P〈0.05）, and that in group C was significantly lower than that in group B （P〈0.05）. Conclusion Angiotensin Ⅱ inhibitor can improve the renal function in CRF rats induced by 5/6（A/I）, which might be associated with HIF-1a signaling pathway.

关 键 词：缺氧诱导因子1 Α亚基 肾纤维化 肾功能衰竭 血管紧张素Ⅱ 缺氧 

分 类 号：R692.5[医药卫生—泌尿科学]