中文摘要：

目的探讨黄芪甲苷（AS-Ⅳ）对高糖（HG）环境下人肾小球系膜细胞（HMCs）增殖和氧化应激损伤保护作用及其可能机制。方法采用MTT方法检测高糖作用不同时间点时及不同浓度AS-Ⅳ干预后HMCs增殖情况;采用实时荧光定量PCR（qPCR）、Western blot方法分别检测不同浓度AS-Ⅳ干预高糖环境下HMCs 48 h后核因子E2相关因子2（Nrf2）、血红素氧合酶1（HO-1）、诱导型一氧化氮合酶（iN-OS）、细胞间黏附分子-1（ICAM-1）mRNA及其蛋白表达;采用过氧化氢（H_2O_2）、总超氧化物歧化酶（T-SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）试剂盒分别检测不同浓度AS-Ⅳ干预高糖环境下HMCs 48 h后细胞上清液中H_2O_2、T-SOD、GSH-Px、MDA含量变化。结果 MTT法结果显示,与正常（NG）组比较,高糖环境下HMCs呈过度增殖趋势（P〈0.05）,不同浓度AS-Ⅳ干预48 h后,与HG组比较,各用药组明显地抑制了高糖环境下HMCs过度增殖且呈剂量依赖性（P〈0.01）;qPCR及Western blot法结果显示,与HG组比较,各用药组明显地增加了Nrf2、HO-1 mRNA及蛋白表达（P〈0.01）,减少了iN OS与ICAM-1 mRNA及蛋白表达（P〈0.05）。各试剂盒测试结果显示,与HG组比较,各用药组明显地降低了HMCs上清液中H_2O_2、MDA的含量（P〈0.05）,增加了HMCs上清液中T-SOD、GSH-Px的含量（P〈0.01）。结论 AS-Ⅳ能够明显地抑制HG环境下HMCs过度增殖。对HG环境下HMCs损伤保护作用的部分机制可能是通过激活Nrf2通路并上调Nrf2、HO-1 mRNA及其蛋白其表达,下调iN OS、ICAM-1 mRNA及其蛋白表达,增加HMCs上清液中T-SOD、GSH-Px的含量,降低HMCs上清液中H_2O_2、MDA的含量。

英文摘要：

Objective To study the effects of astragaloside IV in high glucose-induced proliferation and oxidative stress in HMCs and its mechanism. Methods HMCs were cultured in high glucose with or without different concen- tration of AS-IV. After 48 h, the effect of AS-IV in HMCs proliferation were detected by MTT assay. The mRNA ex- pression and protein levels of Nrf2, HO-1, iNOS, ICAM-1 were determined by qPCR and Western blot, respective- ly. The supernatant were collected to measure the amount of H202,MDA and the activity of T-SOD and GSH-Px. Results Compared with normal group, MTT showed that HMCs significantly increased in high glucose conditions （P 〈0.05）. Compared with high glucose group （HG）, AS-IV significantly inhibited the proliferation of HMCs in dose-dependent manner（P 〈 0. 01 ）. Western blot and qPCR showed that AS-IV increased Nrf2 and HO-1 expres- sion（P 〈 0. 01 ） and suppressed the overexpression of iNOS and ICAM-1 （P 〈 0.05 ） in HMCs in high glucose con- ditions, reduced the amount of H2 02 and MDA（P 〈 0.05）, and increased the activity of T-SOD and GSH-Px（P 〈 0.01 ） in supernatant. Conclusion AS-ivcould significantly inhibit HMCs excessive proliferation in high glucose conditions. The mechanism maybe related to the activating of Nrf2 pathway, upregulating Nrf2, HO-1 protein and mRNA expression, downregulating protein and mRNA expression of iNOS, ICAM-1, increasing in cell supernatant on T-SOD and GSH-Px,reducing H202 and MDA content in the supernatant.