Nrf2-GPX4信号通路与冠心病患者相关性研究  

Correlation between Nrf2⁃GPX4 signaling pathway and patients with coronary heartdisease

作　　者：邢布点 李辉[1] 强甜甜 魏婷[1] 卢园园 康品方[1,2] 张宁汝[1] XING Bu-dian;LI Hui;QIANG Tian-tian;WEI Ting;LU Yuan-yuan;KANG Pin-fang;ZHANG Ning-ru(Department of Cardiology,First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,China;Basic and Clinical Key Laboratory of Cardiovascular and Cerebrovascular Diseases,First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,China;Department of Ophthalmology,First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,China;Bengbu Third People's Hospital Affiliated to Bengbu Medical College,Bengbu 233000,China)

机构地区：[1]蚌埠医学院第一附属医院心内科,安徽蚌埠233000 [2]蚌埠医学院第一附属医院心脑血管疾病基础与临床重点实验室,安徽蚌埠233000 [3]蚌埠医学院第一附属医院眼科,安徽蚌埠233000 [4]蚌埠医学院附属蚌埠市第三人民医院,安徽蚌埠233000

出　　处：《海南医学院学报》2023年第12期905-909,共5页Journal of Hainan Medical University

基　　金：国家自然科学基金资助项目(81970313);蚌埠医学院自然科学重点项目(2020byzd072);蚌埠医学院自然科学重点项目(2020byzd109)。

摘　　要：目的:通过检测血清Nrf2、GPX4活性水平,分析其与冠心病(coronary heart disease,CHD)以及冠脉病变严重程度的相关性,探讨其信号通路介导的铁死亡途径在CHD病情进展中的作用。方法:选取540例疑诊CHD患者,行冠状动脉造影检查,其中360例病人明确诊断为CHD,冠状动脉造影无异常180例为对照组(CON组)。通过ELISA检测CHD患者血清中Nrf2和GPX4活性水平,统计分析在有无CHD血清中Nrf2和GPX4活性差异,Western blot检测CON组和CHD组(各90例)外周血单核细胞(peripheral blood mononuclear cells,PBMCS)Nrf2蛋白的表达,分析其信号通路在CHD患者中的表达意义。结果:CHD组中Nrf2、GPX4活性水平均较对照组降低(P<0.05),且Westernblot检测两组患者PBMCs中Nrf2的表达水平:CHD组Nrf2(0.25±0.05)蛋白表达水平较CON组(0.87±0.16)是呈下调趋势(P<0.05),表明Nrf2蛋白表达水平在CHD患者是低表达的。Pearson相关性分析显示:血清Nrf2、GPX4水平与Gensini评分负相关(Nrf2:r=-0.347,P<0.001;GPX4:r=-0.423,P=0.001)。Nrf2、GPX4与TG负相关(Nrf2:r=-0.284,P<0.001;GPX4:r=-0.275,P=0.001),Nrf2和GPX4水平与LDL呈负相关(Nrf2:r=-0.418,P<0.05;GPX4:r=-0.426,P<0.05),Nrf2和GPX4水平与HDL呈正相关(Nrf2:r=0.318,P<0.05;GPX4:r=0.428,P<0.05),Nrf2与GPX4呈正相关(r=0.456,P<0.01)。结论:Nrf2-GPX4信号通路介导的铁死亡途径与冠脉病变程度及CHD的发病机制有着密切关系,且其作用机制可能与Nrf2-GPX4信号通路表达下调有关。Objective:To analyze the correlation between serum Nrf2 and GPX4 activity levels with coronary heart disease(CHD)and the severity of coronary artery disease,and to explore the role of ferroptosis mediated by its signaling pathway in the progression of CHD.Methods:A total of 540 patients suspected of CHD were selected for coronary angiography,of which 360 pa-tients were diagnosed with CHD.The activity levels of Nrf2 and GPX4 in the serum of CHD patients were detected by ELISA,and the differences in the activities of Nrf2 and GPX4 in the presence or absence of CHD were statistically analyzed.Western blot detection of Nrf2 protein expression of peripheral blood mononuclear cells(PBMCS)in the control(CON)and CHD groups(90 cases each).The expression and significance of its signaling pathway in CHD patients were analyzed.Results:The activity levels of Nrf2 and GPX4 in the CHD group were lower than those in the CON group(P<0.05),and the expression levels of Nrf2 in PBMCs of the two groups were detected by Western blot.The protein expression level of Nrf2 in the CHD group(0.25±0.05)was down-regulated compared with CON group(0.87±0.16)(P<0.05),indicating that Nrf2 protein expression level was low in CHD patients.Pearson correlation analysis showed that serum Nrf2 and GPX4 levels were negatively correlated with Gensini score(Nrf2:r=-0.347,P<0.001;GPX4:r=−0.423,P=0.001).Nrf2 and GPX4 were negatively correlated with TG(Nrf2:r=−0.284,P<0.001;GPX4:r=−0.275,P=0.001),Nrf2 and GPX4 levels were negatively correlated with LDL(Nrf2:r=−0.418,P<0.001)0.05;(GPX4:r=−0.426,P<0.05),Nrf2 and GPX4 levels were positively correlated with HDL(Nrf2:r=0.318,P<0.05;GPX4:r=0.428,P<0.05),and Nrf2 was positively correlated with GPX4(r=0.456,P<0.01).Conclu-sion:The ferroptosis pathway mediated by the Nrf2-GPX4 signaling pathway is closely related to the degree of coronary artery dis-ease and the pathogenesis of CHD,and its mechanism may be related to the down-regulation of the Nrf2-GPX4 signaling pathway.

关 键 词：冠状动脉疾病 病变狭窄程度 NRF2 GPX4 

分 类 号：R541.4[医药卫生—心血管疾病]