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目的观察血糖波动和核转化因子κB(NF-κB)与糖尿病大鼠肾脏病变的关系。方法将SPF级SD大鼠40只,随机分为4组:正常对照组、正常血糖波动组、糖尿病稳定性高血糖组和糖尿病血糖波动组。采用链脲佐菌素(STZ)60 mg/kg腹腔注射建立糖尿病模型。血糖波动组每天8:00和14:00腹部皮下注射胰岛素及灌葡萄糖造成血糖波动模型。实验9周后测定体重、肾指数(KI)、平均血糖(MBG)、每日血糖水平标准差(SDBG)、最大血糖波动幅度(LAGE)、肌酐(Cr)、尿素氮(BUN)、糖化血红蛋白(Hb A1c)、24 h尿微量白蛋白含量,同时用蛋白免疫印迹法测定各组肾脏组织匀浆NF-κB蛋白表达,光镜下观察肾脏组织结构变化。结果正常对照组与正常血糖波动组间各指标差异无统计学意义,糖尿病稳定性高血糖组和糖尿病血糖波动组较正常对照组与正常血糖波动组KI、MBG、SDBG、LAGE、Cr、BUN、Hb A1c、24 h尿微量白蛋白及NF-κB蛋白表达明显升高(P<0.01),体重明显降低(P<0.01);糖尿病血糖波动组与糖尿病稳定性高血糖组比较,差异有统计学意义(P<0.05);肾脏组织形态学观察显示,肾小球体积增大、囊腔扩张破裂,毛细血管内皮细胞基底膜增厚,肾小球细胞减少,炎症细胞浸润,肾小管结构模糊紊乱,糖尿病血糖波动组比糖尿病稳定性高血糖组以上病理变化更为明显。结论血糖波动和NF-κB与糖尿病大鼠肾脏病变的发生发展密切相关。
Objective To observe the relationship between blood glucose fluctuation and nuclear factor-κB (NF-κB) and diabetic nephropathy. Methods Forty Sprague-Dawley (SD) SD rats were randomly divided into four groups: normal control group, normal blood glucose fluctuation group, stable diabetic hyperglycemia group and diabetic hyperglycemic group. The diabetic model was established by intraperitoneal injection of streptozotocin (STZ) 60 mg / kg. Blood glucose fluctuation group every day at 8:00 and 14:00 abdominal subcutaneous injection of insulin and glucose into blood glucose caused by the model. After 9 weeks of experiment, body weight, KI, MBG, SDBG, LAGE, BUN, HbA1c, (Hb A1c) and urinary albumin (24 h). Meanwhile, the protein expression of NF-κB in renal homogenate was determined by Western blotting. The changes of renal tissue were observed under light microscope. Results There was no significant difference between the normal control group and the normal blood glucose fluctuation group, and there was no significant difference in the indexes of KI, MBG, SDBG, LAGE, Cr and BUN between the stable hyperglycemic diabetic group and the diabetic hyperglycemic group compared with the normal control group and the normal blood glucose fluctuation group HbA1c, 24h urinary albumin and NF-κB protein expression was significantly higher (P <0.01), weight was significantly lower (P <0.01); diabetes mellitus group and diabetic stable hyperglycemia group, the difference was statistically significant (P <0.05). Morphological observation of renal tissues showed that glomerular volume increased, cystic dilatation and rupture, capillary basement membrane thickening, glomerular cells decreased, infiltration of inflammatory cells, tubular disorder , Diabetic hyperglycemia group than the stable diabetic hyperglycemia group more obvious pathological changes. Conclusion The fluctuation of blood glucose and NF-κB are closely related to the occurrence and development of nephropathy in diabetic rats.