糖尿病大鼠肾脏组织中氧化应激的实验研究

Experimental study of oxidative stress in the kidneys of diabetic rats

目的探讨糖尿病大鼠肾脏组织中氧化应激水平在糖尿病肾病中的作用。方法采用STZ诱导糖尿病模型鼠。36只大鼠随机分为正常对照组,糖尿病Ⅰ组(给予鱼精蛋白锌胰岛素2~4U/2d),糖尿病Ⅱ组(每日给予鱼精蛋白锌胰岛素9~12U/kg体重)。喂养至12w,测定各组血糖,血中总胆固醇(TC)、甘油三酯(TG)、尿素氮、肌酐、糖化血红蛋白(HbA1c)水平,尿肌酐水平和24h尿蛋白含量。运用比色法测定肾脏皮质中抗氧化酶的活性,包括总超氧化物歧化酶(TSOD)、铜锌超氧化物歧化酶(CuZnSOD)、锰超氧化物歧化酶(MnSOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSHPx),以及丙二醛(MDA)的含量。结果糖尿病Ⅱ组与正常对照组间各指标无显著性差异。糖尿病Ⅰ组与Ⅱ组或正常对照组比较,血糖、TC、TG、HbA1c明显升高;抗氧化酶中,TSOD、CuZnSOD、CAT活性明显下降,GSHPx活性则升高,MnSOD活性在各组中无显著性差异;MDA水平明显升高。尿蛋白含量在糖尿病Ⅰ组较其他两组明显升高,而肌酐清除率则明显下降。结论糖尿病可以引起大鼠肾脏氧化应激水平的升高,在糖尿病肾病发病机制中起重要作用。

Objective To observe changes of oxidative stress in kidneys and their roles in diabetic nephropathy of rats. Methods Diabetic rats were induced by streptozocin (STZ). 36 rats were randomly divided into normal control group (NC group), DⅠgroup〔given protamine zinc insulin (PZI) 2~4 U/2 days〕 and DⅡgroup (given PZI 9~12 U·kg^-1 ·d^-1 ). 12 weeks later, blood glucose, blood cholesterol, trigalloyl glycerol (TG), urea nitrogen, creatinine, HbA1c, urinary creatinine, and urinary protein for 24 hours were measured. The activities of antioxidant enzymes in renal cortex, including total superoxide dismutase (TSOD), Cu-Zn SOD, Mn SOD, catalase (CAT), glutathione peroxidase (GSH-Px), and maleic dialdehyde (MDA) were measured by chromatometry. Results There was no significant difference in all indexes between NC and DⅡgroups. Compared with the other groups, the levels of blood glucose, cholesterol, TG, HbA1c in DⅠgroup increased significantly, the activities of TSOD, Cu-Zn SOD, CAT decreased significantly, but the activity of GSH-Px increased significantly. There was no significant difference in the activities of Mn SOD among three groups. The level of MDA in DⅠgroup was much higher than that in NC or DⅡgroup. Urinary protein in DⅠgroup was significantly higher than that in the other two groups, while creatinine clearance rates decreased significantly. Conclusions Diabetes could cause increase of oxidative stress in kidney of diabetic rats, which play an important role in pathogenesis of diabetic nephropathy.