神经调节蛋白1通过ERK1-2通路减轻心肌细胞缺氧复氧损伤

Neuregulin-1 alleviates hypoxia/reoxygenation injury of cardiomyocytes through ERK1/2 pathway

目的探究神经调节蛋白1(NRG-1)通过细胞外调节蛋白激酶1/2(ERK1/2)通路减轻心肌细胞缺氧复氧(H/R)损伤的作用。方法培养心肌H9c2细胞株,随机分为常规条件下用不含药物DMEM处理的对照组、H/R条件下用不含药物DMEM处理的H/R组、H/R条件下用含NRG-1 DMEM处理的NRG-1组、H/R条件下用含NRG-1及ERK1/2抑制剂PD98059处理的NRG-1+PD组。检测细胞增殖活力、凋亡率及细胞中的凋亡基因、炎症指标、ERK1/2。结果H/R组细胞的OD490水平明显低于对照组,细胞凋亡率、细胞中cleaved Caspase-8、cleaved Caspase-9、cleaved Caspase-3、核因子κB(NF-κB)、ERK1/2的表达水平及培养基中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、γ干扰素(IFN-γ)的含量明显高于对照组;NRG-1组细胞的OD490水平及细胞中ERK1/2的表达水平明显高于H/R组,细胞凋亡率、细胞中cleaved Caspase-8、cleaved Caspase-9、cleaved Caspase-3、NF-κB的表达水平及培养基中TNF-α、IL-1β、IFN-γ的含量明显低于H/R组;NRG-1+PD组细胞的OD490水平及细胞中ERK1/2的表达水平明显低于NRG-1组,细胞凋亡率、细胞中cleaved Caspase-8、cleaved Caspase-9、cleaved Caspase-3、NF-κB的表达水平及培养基中TNF-α、IL-1β、IFN-γ的含量明显高于NRG-1组。结论NRG-1通过激活ERK1/2通路减轻心肌细胞H/R损伤。

Aim To investigate the effect of neuregulin-1(NRG-1)on alleviating hypoxia/reoxygenation(H/R)injury of cardiomyocytes through extracellular regulated protein kinase 1/2(ERK1/2)pathway.Methods Myocardial H9 c2 cell lines were cultured and randomly divided into control group treated with DMEM without drugs under conventional conditions,H/R group treated with DMEM without drugs under H/R conditions,NRG-1 group treated with DMEM containing NRG-1 under H/R conditions,and NRG-1+PD group treated with PD98059 containing NRG-1 and ERK1/2 inhibitors under H/R conditions.Then cell proliferation,apoptosis,apoptosis gene,inflammatory index,ERK1/2 were determined.Results The OD490 level of H/R group was significantly lower than that of control group,the apoptotic rate,the expression levels of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3,nuclear factor kappa B(NF-κB),ERK1/2 in cells and the contents of tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β),interferon gamma(IFN-γ)in culture medium were significantly higher than those of control group.The OD490 level and the expression level of ERK1/2 in cells of NRG-1 group were significantly higher than those of H/R group,and the apoptotic rate,the expression levels of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3,NF-κB in cells and the contents of TNF-α,IL-1β,IFN-γin culture medium were significantly lower than those of H/R group.The OD490 level and the expression level of ERK1/2 in cells of NRG-1+PD group were significantly lower than those of NRG-1 group,and the apoptotic rate,the expression levels of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3,NF-κB in cells and the contents of TNF-α,IL-1β,IFN-γinculture medium were significantly higher than those of NRG-1 group.Conclusion NRG-1 can alleviate H/R injury of cardiomyocytes by activating ERK1/2 pathway.