雷公藤多苷对链脲佐菌素诱导糖尿病肾病大鼠糖基化终末产物特异性受体/细胞核因子-κB信号通路的影响  

Effect of Tripterygium Wilfordii Polyglycosidium on the RAGE/NF-κB Signaling Pathway in Rats with STZ-induced Diabetic Nephropathy

作　　者：徐百升 夏璐[2] 胡春艳 Xu Baisheng;Xia Lu;Hu Chunyan(Blood Purification Center,The First Affiliated Hospital of Henan University,Kaifeng 475000,China;Blood Purification Center,Henan Provincial People＇s Hospital,Zhengzhou 450003,China)

机构地区：[1]河南大学第一附属医院血液净化中心,开封475000 [2]河南省人民医院血液净化中心,郑州450003

出　　处：《成都医学院学报》2018年第3期262-265,共4页Journal of Chengdu Medical College

基　　金：河南省科技计划项目(No:ZDXM20160050)

摘　　要：目的探讨雷公藤多苷(TWP)对链脲佐菌素(STZ)诱导糖尿病肾病(DN)大鼠糖基化终末产物特异性受体/细胞核因子-κB(RAGE/NF-κB)信号通路的影响。方法选取62只6~8周龄的健康SD雄性大鼠,经高糖高脂饮食喂养6周后,再通过腹腔注射STZ 55mg/kg来建立DN大鼠模型,造模成功的大鼠共有60只,按随机数字表法分为DN模型组及TWP低、中、高剂量组(分别为4.5、9、18mg/kg),每组各15只;另选取15只健康SD雄性大鼠作为正常组。于给药8周末,检测大鼠血清生化指标及24h尿蛋白;同时取大鼠肺组织,行蛋白印迹法(Western Blot),测定各组RAGE、NF-κB的表达水平。结果 DN模型组血糖(BG)、血肌酐(Scr)、尿素氮(BUN)及24h尿蛋白水平较正常组升高,经治疗后,TWP治疗组上述指标均较模型组降低,且TWP治疗组上述指标呈剂量依赖性降低,差异有统计学意义(P<0.05)。与正常组比较,DN模型组RAGE和NF-κB蛋白表达水平均增加,TWP治疗组上述蛋白表达量较DN模型组降低,且以TWP高剂量组上述蛋白水平最低,更接近于正常大鼠,差异有统计学意义(P<0.05)。结论 DN的发生发展过程可能与RAGE/NF-κB信号通路激活有关,TWP可通过抑制该信号通路而发挥肾保护作用。Objective To investigate the effect of Tripterygium Wilfordii Polyglycosidium （TWP） on the signal pathway of receptor for advanced glycation end product/nuclear factor-κB （RAGE/NF-κB） in rats with Streptozotocin （STZ） induced diabetic nephropathy （DN）. Methods Sixty-two healthy SD rats aged 6 to 8 weeks were selected and fed on a high-glucose and high-fat diet for 6 weeks. The DN rat model was established by intraperitoneal injection of streptozotocin 55 mg/kg. 60 successful rat models were obtained. The DN rat models were divided into the DN model group, and the low, medium and high dose TWP groups （4.5 mg/kg, 9 mg/kg and 18 mg/kg） respectively according to the random number table method, and each group consisted of 15 DN rat models. Another 15 healthy SD male rats were selected into the normal group. The serum biochemical indexes and 24h urinary protein were detected at the end of 8-week administration. At the same time, the lung tissues of the rats in each group were taken to determine the expression levels of RAGE and NF-κB by Western blot. Results The levels of blood sugar （BG）, serum creatinine （SCR）, urea nitrogen （BUN） and 24h urinary protein in the DN model group were higher than those in the normal group, and the levels of those indexes in the TWP groups were lower than those in the DN model group after treatment and they were decreased in a dose-dependent manner. All those differences were statistically significant （ P 〈0.05）. The protein expression levels of RAGE and NF-κB in the model group increased compared with the normal group, and those in the TWP groups decreased compared with the model group. In the high dose TWP group, the protein expression level was the lowest and close to that of the normal rat, and the difference was statistically significant （ P 〈0.05）. Conclusion The pathogenesis of DN may be related to the activation of the RAGE/NF-κB signaling pathway. TWP can play a role in renal protection by inhibiting this signaling pathway.

关 键 词：雷公藤多苷 STZ 糖尿病肾病 RAGE/NF-κB信号通路 

分 类 号：R332[医药卫生—人体生理学]