17β-雌二醇抗心肌细胞氧化应激损伤的Nrf2/HO-1信号通路的分子机制  

17β-estradiol protects H_9C_2 cardiomyocytes from H_2O_2-induced injury via Nrf2/HO-1 signaling pathway

作　　者：杨静[1] 黎洁[1] 卢长喜 郭爱华[2] 刘长青[1] 杨华 石慧武 牛若颖 

机构地区：[1]唐山市工人医院,河北唐山063000 [2]唐山工人医院康复医疗中心,河北唐山063000 [3]唐山市二十二冶医院,河北唐山063000 [4]唐山市路北区食品药品监督管理局,河北唐山063000

出　　处：《华西药学杂志》2013年第5期467-470,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的观察17β-雌二醇(E2)对H2O2诱导的心肌细胞氧化应激损伤的保护作用,探讨其可能的分子机制。方法将细胞分为对照组、H2O2组、E2组、抑制剂组。用MTT法观察心肌细胞的活性;用Western Blot技术检测Nrf 2的蛋白表达;用RT-PCR技术观察Nrf 2下游靶基因HO-1的mRNA水平。结果 100μmol·L-1H2O2可使H9C2细胞活性显著下降,E2预处理可有效阻止H2O2诱导的心肌细胞损伤;Nrf 2的蛋白表达自E2和H2O2共同培育2 h时即显著高于对照组,6 h达到最高峰;E2也诱导了H2O2处理后H9C2细胞HO-1 mRNA水平及其蛋白表达的升高;ICI 182,780明显逆转了E2的心肌保护作用。结论 E2可有效降低H2O2诱导的心肌细胞损伤,Nrf 2/HO-1信号通路的上调可能是其重要的分子机制。OBJECTIVE To investigate the protective role of 17β-estradiol （E2 ） on myocardial cell injury induced by H2 02 and the possible mechanism. METHODS The oxidative stress model of H9C2 was induced by H202 and the all model were divided into control group, H2 02 group, E2 - treated group and inhibitor group. Myocardial cell viability was detected by MTF assay, as well as Nrf 2 and HO - 1 protein expressions were investigated by Western Blot analysis. RESULTS Compared with control group, 100 μmol. L-l H202 significantly decreased the HgC2 viability and pretreatment of E2 almost prevented the oxidative stress injury. Nrf 2 protein expression gradually increased from E2 - treatment for 2 h with a peak at 6 h compared with H2 02 - treated alone for 4 h or 6 h group. Furthermore the change of HO - 1 mRNA expression shared a similar trend with that of Nrf 2. However, ICI 182,780 almost completely abolished the protective role of E2 which was induced by H2 02 on the oxidative stress injury. CONCLUSION E2 can prevent oxidative stress injury induced by H2 02 and upregulating the Nrf 2/HO - 1 protein expression may be the core molecular mechanism.

关 键 词：H2O2 H9C2细胞 17Β-雌二醇 Nrf 2 HO-1 氧化应激 

分 类 号：R96[医药卫生—药理学]