淫羊藿苷对ApoE^(-/-)小鼠动脉粥样硬化易损斑块细胞凋亡和Nrf2/ARE通路的影响

Effect of epimedium on apoptosis and Nrf2/ARE pathway in atherosclerotic vulnerable plaque of ApoE^(-/-) mice

目的研究淫羊藿苷对载脂蛋白E(apolipoprotein E,ApoE)^(-/-)小鼠动脉粥样硬化易损斑块细胞凋亡及核因子E2相关因子2(nuclear factor E2-related factor 2,Nrf2)/抗氧化反应元件(anti-oxidative response element,ARE)通路的调控作用。方法ApoE^(-/-)小鼠随机分为对照组、模型组和淫羊藿苷组,采用高脂喂养+右侧颈总动脉外置管术(perivascular carotid collar placement,PCCP)制备动脉粥样硬化易损斑块模型,给予淫羊藿苷灌胃干预。检测右侧颈总动脉病理改变,血管平滑肌细胞凋亡,Bcl-2、Bax、Caspase-3、Nrf2和ARE的表达水平及MDA、8-OHdG和TAC的水平。结果与对照组比较,模型组出现了典型的易损斑块病理改变,细胞凋亡率,Bax、Caspase-3的表达水平及MDA和8-OHdG的水平明显升高,Bcl-2、Nrf2和ARE的表达水平及TAC的水平明显降低(P<0.05);与模型组比较,淫羊藿苷组斑块缩小且趋于稳定,细胞凋亡率,Bax、Caspase-3的表达水平及MDA和8-OHdG的水平明显降低,Bcl-2、Nrf2和ARE的表达水平及TAC的水平明显升高(P<0.05)。结论淫羊藿苷能够改善ApoE^(-/-)小鼠的动脉粥样硬化易损斑块,此作用与抑制细胞凋亡及Nrf2/ARE通路有关。

Objective To study the regulatory effects of epimedium on apoptosis and nuclear factor E2-related factor 2(Nrf2)/anti-oxidative response element(anti-oxidant response element,ARE)in atherosclerotic vulnerable plaque of apolipoprotein E(ApoE)^(-/-) mice.Methods ApoE^(-/-) mice were randomly divided into control group,model group and epimedium group.The atherosclerotic vulnerable plaque model was established by high-fat feeding and right common carotid artery catheterization(perivascular carotid collar placement,PCCP),and epimedium was given by gavage.The pathological changes of right common carotid artery,apoptosis of vascular smooth muscle,the expression levels of Bcl-2,Bax,Caspase-3,Nrf2,ARE and the levels of MDA,8-OHdG,and TAC were detected.Results Compared with the control group,the model group showed typical pathological changes of vulnerable plaque,the apoptosis rate,the expression levels of Bax,Caspase-3 and the levels of MDA,8-OHdG significantly increased,the expression levels of Bcl-2,Nrf2,ARE and the level of TAC significantly decreased(P<0.05);Compared with the model group,the plaque of epimedium group was reduced and tended to be stable,the apoptosis rate,the expression levels of Bax,Caspase-3 and the levels of MDA,8-OHdG significantly decreased,the expression levels of Bcl-2,Nrf2,ARE and the level of TAC significantly increased(P<0.05).Conclusion Epimedium improves atherosclerotic vulnerable plaque of ApoE^(-/-) mice,which is related to the inhibition of apoptosis and Nrf2/ARE pathway.