Objective To observe the effect of Tripterygium glycosides (TG) on the expression of hypoxia-inducible factor-1αand endothelin-1 in the kidney of diabetic rats and explore the possible mechanism underlying the protective effect of TG against diabetic nephropathy. Method Sixty 8-week-old male SD rats were randomly divided into normal control group (n=10) and streptozotocin-induced diabetes mellitus (DM) model group (n=50). The diabetic model rats were then randomly divided into DM group, low-dose (8 mg/kg) and high-dose (16 mg/kg) TG treatment groups, and Irbesartan (50 mg/kg) treatment group. After 8 weeks, the levels of blood glucose (BG), 24-h urine protein (24 h Upro), serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. The pathological changes in the renal tissues were examined by optical microscopy, and the mean glomerular area (MGA) and mean glomerular volume (MGV) were measured with pathological image analysis. Immunohistochemical and Western blotting were used to detect the expression of HIF-1αand ET-1 protein in the renal tissue, and their mRNA expressions were detected using real-time fluorescence quantitative PCR. Results HIF-1α and ET-1 expression increased in the kidney of diabetic rats. Compared with the diabetic model rats, the rats receiving TG and Irbesartan treatment showed decreased levels of Scr, BUN, 24h Upro, MGA and MGV, improved renal histopathology, and reduced expression of HIF-1αand ET-1 mRNA and protein in the renal tissue. These changes were more obvious in high-dose TG treatment group. Correlation analysis showed that the expression of HIF-1α was positively correlated with that of ET-1, and they were both positively correlated with kidney weight index (KW/BW), 24 h Upro, MGA, and MGV. Conclusion HIF-1αand ET-1 are overexpressed in the kidney of diabetic rats. TG can improve kidney damage in diabetic rats and delay the development of diabetic nephropathy by inhibiting the HIF-1αand ET-1 expression.%目的：研究雷公藤多苷对糖尿病大鼠肾组织缺氧诱导因子-1α（HIF-1α）及内皮素-1（ET-1）表达的影响，探讨雷公藤多苷对糖尿病大鼠肾脏损伤的保护作用及可能机制。方法采用链脲佐菌素（55 mg/kg体质量）诱导致糖尿病大鼠，动物分为正常对照组，糖尿病对照组，雷公藤多苷低、高剂量治疗组（8、16 mg/kg）及阳性对照组（厄贝沙坦50 mg/kg），灌胃给药，每日1次，8周末检测大鼠空腹血糖（BG），血肌酐（Scr），尿素氮（BUN），24 h尿蛋白（24 h Upro）；HE染色光镜观察肾组织形态学的改变；病理图像分析系统分析平均肾小球面积（MGA）及平均肾小球体积（MGV）；免疫组织化学及Western blot检测肾组织HIF-1α及ET-1蛋白表达；实时荧光定量PCR检测肾组织HIF-1α及ET-1mRNA表达。结果糖尿病大鼠肾组织HIF-1α及ET-1表达增高。与糖尿病对照组比较，各治疗组大鼠Scr、BUN、24 h Upro、肾重指数（KW/BW）、MGA、MGV显著降低，肾组织病理形态学明显改善；HIF-1α、ET-1mRNA及蛋白表达显著减少；雷公藤多苷高剂量组各指标改善较显著。相关性分析显示ET-1表达与HIF-1α表达呈正显著相关，HIF-1α及ET-1mRNA及蛋白表达与肾重指数（KW/BW）、24 h Upro、MGA、MGV呈显著正相关。结论糖尿病大鼠肾组织HIF-1α及ET-1表达增加，雷公藤多苷可通过抑制HIF-1α及ET-1的表达，改善糖尿病大鼠肾脏损害，延缓糖尿病肾病的发生发展。
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