缺氧诱导因子1α介导的信号通路在血管紧张素Ⅱ诱导肾间质纤维化中的作用  

Role of hypoxia inducible factor 1α-mediated signaling pathway in angiotensin Ⅱ- induced renal interstitial fibrosis

作　　者：唐琳[1] 郭青[1] 张翠翠[1] 刘章锁[1] 张晓雪[1] 

机构地区：[1]郑州大学第一附属医院肾内科,450052

出　　处：《中华肾脏病杂志》2011年第3期194-197,共4页Chinese Journal of Nephrology

摘　　要：目的探讨缺氧诱导因子1α（HIF-1α）介导的信号通路在血管紧张素Ⅱ（AngⅡ）诱导肾间质纤维化（RIF）中的作用。方法体外培养肾小管上皮细胞，以不同浓度（10^-9～10^-6mol／L）的AngⅡ分别处理24h、48h时，用实时荧光定量PCR和Western印迹法分别检测肾小管上皮细胞中HIF-1α、脯氨酸羟化酶2（PHD2）及基质金属蛋白酶1组织抑制剂（TIMP-1）mRNA和蛋白的表达变化情况。结果随AngⅡ刺激浓度的增加，HIF。letmRNA的表达水平也增加，呈浓度依赖性。当AngⅡ浓度在10^-7mol／L，并且干预时间为24h时，HIF-1αmRNA的表达水平增加了166％。实时荧光定量PCR和Western印迹分析显示，相对于空白对照组，在AngⅡ干预的肾小管上皮细胞中HIF-1α、TIMP-1的mRNA和蛋白表达水平均升高（P〈0．05），而PHD2的mRNA和蛋白表达水平均下降（P〈0．05）。结论AngⅡ可能通过下调PHD2的表达而减少肾小管上皮细胞中HIF-1α的降解，从而上调HIF-1α及TIMP-1的表达，参与RIF。Objective To explore the role of hypoxia inducible factor 1α （HIF-1α）- mediated signaling pathway in angiotensin Ⅱ （Ang Ⅱ ） induced renal＇ interstitial fibrosis. Methods Renal tubular epithelial cells were cultured and treated with different concentrations （10^-9-10^-6 mol/L） of Ang Ⅱ for 24 h and 48 h. Real-time quantitative PCR and Western blotting were preformed to detect the mRNA and protein expressions of HIF-1α, prolyl hydroxylase 2 （PHD2） and tissue inhibitor of metalloproteinase 1 （TIMP-1） in renal tubular epithelial cells. Results HIF-1α mRNA level was increased with Ang Ⅱ treatment in a concentration dependent manner. When ceils were treated with Ang Ⅱ concentration at 10^-7 mol/L for 24 h, the mRNA level was markedly increased by 166%. Furthermore, by real-time quantitative PCR and Western blotting, compared with the control group, AngⅡ increased the mRNA and protein levels of HIF-1α and TIMP-1 （P〈 0.05, respectively）, while the mRNA and protein levels of PHD2 were decreased markedly （P〈 0.05, respectively） in renal tubular epithelial cells. Conclusion Ang Ⅱ reduces HIF-1α degradation in renal tubular epithelial ceils probably by reducing the expression of PHD2, which increases the expressions of HIF-1α and TIMP-1 involved in renal interstitial fibrosis.

关 键 词：血管紧张素Ⅱ 纤维化 缺氧诱导因子1α亚基 肾小管上皮细胞 脯氨酸羟化酶2 基质金属蛋白酶1组织抑制剂 

分 类 号：R285.5[医药卫生—中药学]