黄芪甲苷对2型糖尿病肾病大鼠肾组织PI3K/Akt/FoxO1信号调控的影响

被引：156

作者：

马可可 ^{[1
]}

鞠营辉 ^{[1
]}

陈清青 ^{[1
]}

李维祖 ^{[1
]}

李卫平 ^{[2
]}

机构：

[1] 安徽医科大学基础医学院

[2] 安庆医药高等专科学校

来源：

中国实验方剂学杂志 | 2019年 / 25卷 / 02期

关键词：

糖尿病肾病; 黄芪甲苷; 磷酯酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/叉头框转录因子O亚族1(FoxO1)信号通路; 自噬;

D O I：

暂无

中图分类号：

R285.5 [中药实验药理];

学科分类号：

100806 [中药药理学];

摘要：

目的:研究黄芪甲苷对2型糖尿病肾病大鼠肾脏的保护作用及其对磷酯酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/叉头框转录因子O亚族1（FoxO1）信号的调控作用,探讨黄芪甲苷保护2型糖尿病肾病的机制。方法:6周高糖高脂饮食后,给予链脲佐菌素（STZ）一次性腹腔注射(35 mg·kg-1)建立2型糖尿病大鼠模型,随机分为正常组,模型组,黄芪甲苷(20,40,80 mg·kg-1)组及盐酸二甲双胍（阳性药）组。连续给药8周后检测各组大鼠体质量,肾脏指数,血糖,24 h尿蛋白,尿微量白蛋白,尿肌酐,血肌酐及血尿素氮含量的变化;苏木素-伊红（HE）染色观察肾脏组织病理形态学变化;马松（Masson）三色染色观察胶原表达水平;过碘酸六胺银（PASM）染色观察基底膜的变化;免疫组化检测磷酸化FoxO1（p-FoxO1）蛋白表达;蛋白质免疫印迹法（Western blot）分析PI3K/Akt/FoxO1信号蛋白及自噬标记蛋白PI3K,微管相关蛋白1轻链3（LC3）Ⅰ/Ⅱ,B细胞淋巴瘤-2（Bcl-2）/腺病毒E1B 19 k Da相互作用蛋白3（BNIP3）,Beclin1,p-Akt,Akt表达水平。结果:与正常组比较,模型组肾小球基底膜增厚,细胞外基质增多,系膜扩张,胶原蛋白显著增加,PI3K/Akt/FoxO1信号增强（P <0. 01）,自噬活性减弱（P <0. 01）;与模型组比较,黄芪甲苷中、高剂量肾脏组织病变明显改善,明显抑制肾组织PI3K,Akt及FoxO1磷酸化水平（P <0. 05,P <0. 01）,同时增强自噬反应,上调BNIP3,LC3Ⅱ/LC3Ⅰ和Beclin1的表达（P <0. 05,P <0. 01）。结论:黄芪甲苷可能通过抑制PI3K/Akt/FoxO1信号增加肾组织细胞自噬活性,减缓了2型糖尿病肾病的发展进程。

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页码：74 / 81

页数：8

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