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发育性内皮基因座-1在人冠状动脉粥样硬化斑块中的表达及其与冠心病的关系

Expression of developmental endothelial locus-1 gene in human coronary atherosclerotic plaques and its correlation with coronary heart disease
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摘要 目的 检测发育性内皮基因座-1(DEL-1)在人冠状动脉粥样硬化斑块中的表达,探讨其参与冠心病(CHD)发生发展的相关机制。方法 将58例人冠状动脉标本分为CHD组(25例)和对照组(CON组,33例),以左前降支作为研究对象;通过HE染色检测冠状动脉内膜厚度、纤维帽厚度、管腔狭窄程度评价冠状动脉结构改变;Western blot法检测冠状动脉内DEL-1、白细胞介素-17(IL-17)、糖原合成酶激酶-3β(GSK-3β)、磷酸化糖原合成酶激酶-3β(p-GSK-3β)及CCAAT增强结合蛋白β(C/EBPβ)的表达水平;免疫组织化学染色方法检测DEL-1、GSK-3β、C/EBPβ及IL-17在动脉粥样硬化斑块内的细胞分布及表达水平;Pearson积矩相关系数检验分析DEL-1表达水平与冠状动脉形态结构变化之间的相关性。结果 HE结果显示,与CON组相比,CHD组血管内膜增厚、管腔狭窄程度增大、纤维帽厚度变薄(P<0.05);免疫组织化学染色显示,CHD组中DEL-1主要表达在斑块内泡沫细胞胞质及胞核,而IL-17、GSK-3β及C/EBPβ主要在胞质中表达;Western blot结果显示,与CON组比较,CHD组中DEL-1、IL-17、GSK-3β、p-GSK-3β、C/EBPβ表达水平升高(P<0.05);Pearson积矩相关系数结果显示,DEL-1的蛋白表达水平与血管内膜厚度、管腔狭窄程度呈正相关(r=0.693、0.733,P<0.05),与纤维帽厚度呈负相关(r=-0.432,P<0.05)。结论 DEL-1在人动脉粥样硬化斑块内表达增加,其可能通过GSK-3β/C-EBPβ通路调节斑块内炎症反应,从而参与CHD的发生发展。 Objective To detect the expression of developmental endothelial locus-1(DEL-1)in human coronary atherosclerotic plaques,to investigate the mechanism of its involvement in the development of coronary heart disease.Methods Fifty-eight human coronary artery specimens were divided into coronary heart disease group(CHD,25 cases)and control group(CON,33 cases).The left anterior descending branch was taken as the object of study.The structural changes of coronary arteries were evaluated by HE staining on coronary artery intima thickness,fibrous cap thickness and lumen stenosis degree.The expression levels of DEL-1,interleukin-17(IL-17),glycogen synthase kinase-3β(GSK-3β),phosphorylated glycogen synthase kinase-3β(p-GSK-3β)and CCAAT enhanced binding proteinβ(C/EBPβ)in coronary arteries were detected by Western blot.The expression and distribution of DEL-1,GSK-3β,C/EBPβ,and IL-17 in atherosclerotic plaques were detected by immunohistochemical staining,and the correlation between DEL-1 expression and coronary artery structure was analyzed by Pearson moment correlation coefficient test.Results HE results showed that compared with the CON group,the intima of vessels in the CHD group was thickened,the degree of lumen narrowing increased,and the thickness of the fibrous cap thinned(P<0.05);immunohistochemical staining results showed that DEL-1 was mainly expressed in the cytoplasm and nucleus of foam cells within the plaques in the CHD group,whereas IL-17,GSK-3β,and C/EBPβwere mainly expressed in the cytoplasm.Western blot results indicated the expression levels of DEL-1,IL-17,GSK-3β,p-GSK-3β,and C/EBPβwere elevated in the CHD group compared with CON group(P<0.05).Pearson moment correlation coefficients showed that the protein expression level of DEL-1 was positively correlated with intima-media thickness and luminal stenosis,and negatively correlated with fibrous cap thickness(r=0.693,0.733;P<0.05),and negatively correlated with thickness of the fibrous cap(r=-0.432,P<0.05).Conclusion DEL-1 expression is increased within human atherosclerotic plaques and might be involved in the development of coronary heart disease by regulating the intraplaque inflammatory response through the GSK-3β/C-EBPβpathway.
作者 路艳林 周明 李曼 彭进 戴佳琳 丁九阳 万昌武 汪家文 王杰 夏冰 LU Yanlin;ZHOU Ming;LI Man;PENG Jin;DAI Jialin;DING Jiuyang;WAN Changwu;WANG Jiawen;WANG Jie;XIA Bing(Department of Forensic Medicine,Guizhou Medical University,Guiyang 550004,Guizhou,China;School of Basic,Medicine Medicine&Technology College of Zunyi Medical University,Zunyi 564600,Guizhou,China;Department of Forensic Medicine,Zunyi Medical University,Zunyi 564600,Guizhou,China)
出处 《贵州医科大学学报》 CAS 2024年第1期34-40,共7页 Journal of Guizhou Medical University
基金 国家自然科学基金(82060340) 贵州省科技计划项目(黔科合基础-ZK[2021]一般487) 贵州医科大学国家自然科学基金培育项目(20NSP083)。
关键词 发育性内皮基因座-1 冠心病猝死 白细胞介素-17 糖原合成酶激酶-3β/CCAAT增强结合蛋白β通路 炎症反应 动脉粥样硬化 developmental endothelial locus-1 sudden coronary death interleukin-17 GSK-3β/C-EBPβpathway inflammatory response atherosclerosis
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