【摘要】  目的  评价氧化应激（OS）在血糖波动加速DN发病过程中的作用。  方法  16只雄性GK大鼠随机分为持续高血糖（MS）组与血糖波动（MF）组，另8只雄性Wistar大鼠作为正常对照（NC）组。MF组每日错时腹腔注射葡萄糖及皮下注射胰岛素造成血糖波动模型，MS组每日错时腹腔注射葡萄糖造成持续高血糖模型，NC组每日错时腹腔注射等剂量生理盐水，连续6周。每日观察大鼠的一般体征，第6周末检测全日9个时间点的血糖。麻醉处死大鼠，心脏采血，检测血清中肌酐（Scr）、尿酸（SUA）、TC、TG等指标的含量；取双侧肾脏，称重，计算肾脏指数；检测肾组织与肾组织线粒体中OS水平，包括丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）的含量；HE染色，光镜下观察大鼠肾脏病理变化。  结果  与NC组相比，MS组与MF组体重增长速度减慢，肾脏指数、Scr、SUA、TC、TG、肾组织与肾组织线粒体中MDA升高（P＜0.05或P＜0.01），肾组织与肾组织线粒体中SOD与GSH-Px降低（P＜0.05或P＜0.01），肾脏病理改变严重；与MS组相比，MF组肾脏指数、Scr、SUA、TC、肾组织与肾组织线粒体中MDA、SOD、GSH-Px等指标及肾脏病理上的变化更明显（P＜0.05或P＜0.01）。  结论  OS水平在糖尿病大鼠肾组织与肾组织线粒体中增强，其在血糖波动加速DN发病过程中发挥重要作用。

【关键词】  GK大鼠；血糖波动；氧化应激；糖尿病肾病

 Role of oxidative stress in the process of blood glucose fluctuation  acce-lerating  the development of diabetic nephropathy in GK rats

【Abstract】  Objective  To evaluate the role of oxidative stress (OS) in the process of blood glucose fluctuation accelerating the development of diabetic nephropathy in GK rats.  Methods  A total of 16 male GK rats were selected and divided into two groups: sustained high blood glucose group (MS group) and blood glucose fluctuation group (MF group). Another 8 male Wistar rats were selected as normal control group (NC group). GK rats in MF group were intraperitoneally injected with glucose and subcutaneously injected with insulin at different time points every day for 6 weeks. GK rats in MS group were intraperitoneally injected with glucose at different time points every day for 6 weeks. Rats in NC group were injected intraperitoneally with isodose physiological saline at different time points every day for 6 weeks. General physical signs of rats were observed daily, and blood glucose at nine time points of the last day of week 6 was tested. Rats were executed after anesthesia. Contents of serum creatinine (Scr), uric acid (UA), total cholesterol (TC) and triglyceride(TG) were detected in the blood drawn from heart; renal index was calculated after both kidneys were weighed; levels of oxidative stress in kidney and renal mitochondria were detected including contents of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px); the kidney was observed under light microscope for pathological change after HE staining.  Results  Compared with NC group, weight growth were significantly slowed in MS and MF group; renal index, Scr, SUA, TC, TG and MDA in kidney and renal mitochondria increased significantly(P＜0.05 or P＜0.01),and SOD and GSH-Px in kidney and renal mitochondria decreased significantly(P＜0.05 or P＜0.01), and renal pathological change was more serious. Compared with MS group, renal index, Scr, SUA, TC and MDA, SOD and GSH-Px in kidney and renal mitochondria, as well as renal pathology changed more obviously in MF group (P＜0.05 or P＜0.01).  Conclusion  Oxidative stress in diabetic rats kidney and renal mitochondria were significantly enhanced, suggesting oxidative stress playing an important role in the process of blood glucose fluctuation accelerating the development of diabetic nephropathy.

【Key Words】  GK rat； Blood glucose fluctuation； Oxidative stress（OS）；Diabetes nephropathy（DN）