摘要
目的探讨糖尿病肾病与核因子-Kappa B(NF-κB)表达的关系,进一步研究还原型谷胱甘肽(GSH)对NF-κB活性的影响及其对糖尿病肾脏病变的防治作用。方法70只雄性SD大鼠随机分为对照组(10只)和糖尿病组60只(1月组、3月组、6月组及相对应干预组各10只)。糖尿病模型组和干预组按60mg/kg剂量一次性腹腔内注射链脲菌素,对照组仅腹腔内注射同样体积的0.1mmol/L柠檬酸缓冲液。3d后测空腹血糖≥16.5mmol/L为糖尿病造模成功,干预组在造模成功后予GSH(按10mg/100g计算),每日腹腔注射1次。每周测大鼠血糖、体质量等指标;分别于1、3、6月末处死大鼠,留取肾脏标本,提取核蛋白,同位素探针标记后,以EMSA法测定NF-κB表达,同时作电泳条带灰度分析。结果EMSA电泳条带光密度分析结果显示:与正常对照组相比,糖尿病各组NF-κB表达均增强(P<0.05);糖尿病1、3、6月组NF-κB表达随病程延长呈现逐渐增强趋势;干预组与相对应各组比较NF-κB表达显著减弱(P<0.05)。结论进一步证实了NF-κB活化在糖尿病发生、发展中的作用,并通过GSH干预治疗,有效抑制了NF-κB的活化,从而达到抑制炎症反应的目的。
objective To investigate the relation between diabetic nephropathy and nuclear factor-KB （NF-κB） expression, and observe the effect of reduced glutathione sodium （GSH） on NF-κB activation and in prevention of diabetic nephropathy. Methods Seventy male Sprague-Dawley rats weighing 200±25 g were randomized into control group （10 rats） and diabetic group （60 rats, subgrouped into 1 month, 3 months, 6 months and their corresponding intervention subgroups, each consisting of 10 rats）. The rats in the 6 diabetic groups were subjected to intraperitoneal injection of streptozotucin, and those in the control group received injection with 0.1 mmol/L citric acid buffer solution of the same volume. The diabetic models were affirmed upon a fasting blood glucose ≥ 16.5 mmol/L 3 days after the injection. The intervention groups were injected intraperitoneally with GSH （10 mg/100 g） once daily. Fasting blood glucose and body weight were measured every week. The rats were executed at the end of 1, 3, and 6 months respectively and the nucleoproteins were extracted from the renal specimen. NF-κB was measured using electrophoretic mobility shift assay （EMSA） after labeling with isotope probe, and the gray scale of the electrophoretic bands was analyzed. Results EMSA optical density analysis of electrophoretic bands showed that NF-KB expression increased in each diabetic groups in comparison with the control group （P〈0.05）, and NF-κB level rose proportionally with the disease course of I month, 3 months and 6 months. The activity of NF-κB decreased in the intervention groups as compared with the corresponding untreated groups （P〈0.05）. Conclusion The activation of NF-κB plays a role in the onset and development of diabetes. NF-κB inhibition and containment of inflammation might be one of the mechanisms of GSH treatment for diabetes.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2007年第3期332-335,共4页
Journal of Southern Medical University
关键词
糖尿病
糖尿病肾病
还原型谷胱甘肽
核因子-ΚB
diabetes
diabetic nephropathies
nuclear factor-κB
reduced glutathione sodium
