铜死亡诱导剂FDX1、硫辛酸与冠状动脉病变严重程度的相关性  

Correlation of serum ferredoxin 1 and lipoic acid levels with severity of coronary artery disease

作　　者：魏婷 丁洋洋 张佳佳 李金龙 张恒 康品方 张宁汝 WEI Ting;DING Yangyang;ZHANG Jiajia;LI Jinlong;ZHANG Heng;KANG Pinfang;ZHANG Ningru(Department of Cardiovascular Medicine of First Affiliated Hospital,Bengbu Medical University,Bengbu 233000,China;Key Laboratory of Preclinical and Clinical Cardiovascular Medicine,Bengbu Medical University,Bengbu 233000,China)

机构地区：[1]蚌埠医科大学第一附属医院心血管科,安徽蚌埠233000 [2]蚌埠医科大学心脑血管基础与临床重点实验室,安徽蚌埠233000

出　　处：《南方医科大学学报》2024年第2期308-316,共9页Journal of Southern Medical University

基　　金：安徽省高校科学研究优秀青年项目(2022AH030141);安徽省高校蚌埠医学院研究生创新计划(Byycx22109);安徽省重点研究与开发计划青年项目(202304295107020079);安徽省优秀科研创新团队项目(2022AH010083)。

摘　　要：目的分析铜死亡诱导剂铁氧还蛋白1(FDX1)、硫辛酸(LA)与冠状动脉粥样硬化发病以及不同病变程度之间的相关性,探讨二者在冠心病(CHD)发生、发展中的变化规律。方法选取冠脉造影(CAG)提示冠脉病变患者和CAG正常患者,其中冠脉病变患者按照冠脉狭窄严重程度分成轻度狭窄组(a-CHD组)、中度狭窄组(b-CHD组)和严重狭窄组(c-CHD组)。通过酶联免疫吸附法(ELISA)检测不同冠脉狭窄患者和正常患者血清FDX1、LA水平。以ApoE-/-小鼠为高脂血症小鼠模型,通过HE染色检测正常小鼠和模型小鼠主动脉病理形态学变化;天狼猩红染色观察胶原纤维沉积情况;免疫组化检测主动脉FDX1、LA的表达与分布,RT-PCR检测小鼠主动脉FDX1、硫辛酸合成酶(LIAS)和线粒体顺乌头酸酶(ACO_(2))mRNA表达。结果与对照组相比,a-CHD组、b-CHD组和c-CHD组血清FDX1、LA水平均明显降低(P<0.05,P<0.01),随着冠脉狭窄程度的加重血清FDX1、LA水平逐渐减低(P<0.01);随着冠脉病变支数的增加FDX1、LA逐渐下降(P<0.05,P<0.01);血清FDX1、LA水平与Gensini评分呈明显负相关关系(r=-0.241,P<0.01;r=-0.273,P<0.01),血清FDX1与LA呈正相关关系(r=0.451,P<0.01)。与正常小鼠相比,ApoE-/-模型组小鼠血脂水平明显上升(P<0.01),动脉粥样硬化(AS)指数明显增高,ApoE-/-模型组主动脉血管有增厚及脂质聚集、血管胶原纤维增生明显,FDX1、LA、LIAS、ACO_(2)表达均明显降低(P<0.05,P<0.001)。结论随着不同冠状动脉病变程度的加剧,血清FDX1、LA水平逐渐降低,且两者之间存在相关性,FDX1、LA的表达与高脂血症所致的血管病变有关。Objective To analyze the correlation of copper death inducer ferredoxin 1(FDX1)and lipoic acid(LA)with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease(CHD).Methods We analyzed the data of 226 patients undergoing coronary artery angiography(CAG)in our hospital between October,2021 and October,2022,including 47 patients with normal CAG findings(control group)and 179 patients with mild,moderate or severe coronary artery stenosis(CHD group).Serum FDX1 and LA levels were determined with ELISA for all the patients.We also examined pathological changes in the aorta of normal and ApoE-/-mice using HE staining and observed collagen fiber deposition with Sirius red staining.Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta,and RT-PCR was performed to detect the expressions of FDX1,LIAS and ACO_(2) mRNAs in the myocardial tissues.Results Compared with the control patients,CHD patients had significantly lower serum FDX1 and LA levels,which decreased progressively as coronary artery stenosis worsened(P<0.01)and as the number of involved coronary artery branches increased(P<0.05).Serum FDX1 and LA levels were positively correlated(r=0.451,P<0.01)and they both negatively correlated with the Gensini score(r=-0.241 and-0.273,respectively;P<0.01).Compared with normal mice,ApoE-/-mice showed significantly increased lipid levels(P<0.01)and atherosclerosis index,obvious thickening,lipid aggregation,and collagen fiber hyperplasia in the aorta,and significantly reduced expressions of FDX1,LA,LIAS,and ACO_(2)(P<0.05).Conclusion Serum FDX1 and LA levels decrease with worsening of coronary artery lesions,and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.

关 键 词：冠状动脉疾病 病变严重程度 高脂血症 铁氧还蛋白1 硫辛酸 

分 类 号：R541.4[医药卫生—心血管疾病]