早期糖尿病大鼠肾脏中HIF-1α表达和细胞凋亡的研究

The Significance of HIF-1α Expression and Cell Apoptosis in the Early Stage of Diabetic Rat Kidney

目的:探讨缺氧诱导因子(HIF)-1α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DN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、免疫印迹和原位缺口末端标记法(TUNEL)染色,连续多时点观察肾脏HIF-1α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:免疫组化、蛋白印迹检测显示DN组2、4、8周HIF-1α的表达均强于对照组,DN组HIF-1α的表达与尿蛋白、肾脏肥大指数(KI,肾质量/体质量)呈正相关;DN组2、4、8周肾小管细胞凋亡指数(AI)均高于对照组,DN组AI与尿蛋白、KI呈正相关。DN组HIF-1α表达量和肾脏细胞AI呈正相关。结论:HIF-1α在早期糖尿病大鼠肾脏中表达上调,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-1α可能诱导细胞凋亡增加,从而促进DN的发展。

Objective： To explore the significance of hypoxia-inducible factor （HIF）-1α expression and cell apoptosis in renal tissues of early-stage diabetic rats, and their relationship with the development of diabetic nephropathy （DN） thereof. Methods： The Sprague-Dawlley （SD） rats were divided into DN group and control group. The rats of DN group were treated by streptozotocin （STZ）. The expression of HIF-1α and renal cell apoptosis in renal tissue was detected by immunohistochem- istry, immunoblotting and TUNEL staining at 2, 4 and 8 weeks after the success of modeling. The relationship was analyzed between HIF-1α, the renal cell apoptosis and renal pathological changes. Results： The expression level of HIF-1α was sig- nificantly higher at 2, 4 and 8 weeks in DN group than that of control group detected by immunohistochemistry and immunob- lotting staining. The expression of HIF-1α was positively related with urine protein and kidney hypertrophy index （KI） in DN group. The renal tubular cell apnptosis index （AI） was higher at 2, 4 and 8 weeks in DN group than that of control group. There was a positive correlation between AI, urine protein and KI. And the level of HIF-1α expression was positively correlated with AI in DN group. Conclusion： The upregulated expression of HIF-1αand the increased apoptosis of renal cells contribute to the development of DN in early-stage DN rats. HIF-1α may induce cell apoptosis and promote the renal injury of diabetes mellitus in rats.