AngⅡ抑制剂对HIF-1α在慢性肾衰大鼠肾组织中表达的影响
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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).


Effects of angiotensin Ⅱ inhibitor on HIF-1α expression in the renal tissue of 5/6th kidney ablation/infarction rats
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Supported by National Natural Science Foundation of China(30973723), Fund of Shanghai Science and Technology Committee(08411962400), and Fund for Building Innovation Team of Shanghai Higher Institutions (201203).

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    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。

    Abstract:

    ObjectiveTo investigate the influences of Angiotensin Ⅱ inhibitor on renal expression of HIF-1α mRNA and protein in the chronic renal failure (CRF) rats (induced by 5/6th kidney ablation/infarction \[5/6A/I\]) and the related mechanism. MethodsSD 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-1α mRNA and protein in the remnant renal cortex and medulla were assessed by Real-time PCR and Western blotting analysis. ResultsCompared 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-1α 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). ConclusionAngiotensin Ⅱ inhibitor can improve the renal function in CRF rats induced by 5/6(A/I), which might be associated with HIF-1α signaling pathway.

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  • 收稿日期:2012-04-08
  • 最后修改日期:2012-06-18
  • 录用日期:2012-09-19
  • 在线发布日期: 2012-09-24
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