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早期糖尿病大鼠肾脏中HIF-1α表达和细胞凋亡的研究

颜晓勇   

  1. 贵州省遵义医学院附院肾病风湿科
  • 收稿日期:2011-01-21 修回日期:2011-04-18 出版日期:2011-10-15 发布日期:2011-10-15
  • 通讯作者: 颜晓勇

The Significance of HIF-1αexpression and Apoptosis in the Kidney of Early- -stage diabetic nephropathy Rats

  • Received:2011-01-21 Revised:2011-04-18 Published:2011-10-15 Online:2011-10-15

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摘要： [摘要] 目的　探讨缺氧诱导因子-1а(HIF-1а)在早期糖尿病大鼠肾脏中表达的变化规律和细胞凋亡与糖尿病肾病(DN)发生发展的关系。方法　实验分为糖尿病模型组和正常对照组。采用链脲佐菌素(STZ)诱导大鼠DN模型,分别于造模成功后2、4、8周,用免疫组化、免疫印迹和TUNEL染色分析连续多时点观察肾脏HIF-1а表达和细胞凋亡情况,并分析两者之间的关系及其与肾脏病理变化指标的相关性。结果 糖尿病组2、4、8周HIF-1а的表达均强于对照组,各时点间也有差异,与尿蛋白、肾重/体重（KI）正相关；糖尿病组2、4、8周肾小管细胞凋亡指数（Index of apoptosis,AI）均高于对照组,各时点间也有差异,与尿蛋白、KI正相关。HIF-1а表达量和肾脏细胞AI也呈正相关。结论 HIF-1а在早期糖尿病大鼠肾脏中表达上调,以肾小管上皮细胞和肾间质细胞中表达上调为主,并随病程逐渐增强,其表达变化与糖尿病大鼠肾脏病变发生发展相关。细胞凋亡也参与了早期DN的发生发展，HIF-1а可能诱导细胞凋亡增加，从而促进DN的发展。

关键词: 糖尿病肾病, 缺氧诱导因子-1а, 细胞凋亡

Abstract: [Abstract] Objective To explore the significance of HIF-1а expression and the apoptosis in the renal tissue of early-stage diabetic rats. Methodes The Sprague- -Dalwley(SD) rats were divided into the diabetic and control groups.Diabetic group was treated by streptozotocin(STZ). The expression of HIF-1а in renal tissue was detected by immunohisochemistry and Western Blot at 2, 4, 8weeks; The apoptosis of renal cell was measured by TUNEL assay at the same time. The level of HIF-1а expression and the renal index of apoptosis (AI) were quantified by computer image analysis.The relationship between HIF-1а and the renal AI, renal/body weight, urinary protein excretion was analyzed. Results HIF-1а staining in the renal tubular and interstitial cells of Early-stage Diabetic Rats was significantly increased at 2,4 and 8 weeks, as compared with control group; The renal tubular and interstitial cells AI was higher than that of control group at the same time points.The level of HIF-1а expression was positively correlated with KI and urine protein excretion, respectively, So was the renal AI. It was found that there was a strong positive correlation between the level of HIF-1а and the renal AI. Conclusion The upregulated expression of HIF-1а and the increased apoptosis of renal cells in early-stage DN rats could contribute to the development of DN. Their interaction may promote the renal injury of diabetes mellitus.

Key words: Diabetic nephropathy, Hypoxia-inducible factor-1а, Apoptosis