冠状动脉粥样硬化患者外周血单个核细胞抗菌肽α防御素和组织蛋白酶抑制素基因的表达变化  

Expression Levels of alpha-Defensins and Cathelicidin are Upregulated in Peripheral Mononuclear Blood Cells of Patients with Coronary Atherosclerosis

作　　者：赵汉军[1] 山下静也[2] 永井义幸 中川理 野岛博[5] 

机构地区：[1]首都医科大学附属北京安贞医院,北京市100029 [2]大阪大学医学部附属病院 [3]临空医疗中心 [4]丰中市立病院 [5]大阪大学微生物病研究所

出　　处：《中国动脉硬化杂志》2010年第3期223-226,共4页Chinese Journal of Arteriosclerosis

基　　金：北京市自然科学基金(7082030);北京市优秀人才基金(20081D0300600080);首都医科大学临床基础合作课题(2007JL42)部分资助

摘　　要：目的探讨外周血单个核细胞抗菌肽α防御素和组织蛋白酶抑制素基因表达水平与冠状动脉粥样硬化的关系。方法冠状动脉粥样硬化性心脏病组61例,为临床症状符合稳定型劳力性心绞痛,且冠状动脉造影发现左主干直径狭窄≥50%,或左前降支、左回旋支和右冠状动脉主支至少一处病变直径狭窄≥75%的患者;对照组53例,为经冠状动脉造影排除冠状动脉粥样硬化性心脏病者。冠状动脉造影前获得空腹静脉血进行血常规和高敏C反应蛋白检测、提取总核糖核酸并合成互补脱氧核糖核酸用于实时定量RT-PCR。结果冠状动脉粥样硬化性心脏病组糖尿病比例(34.4%比15.1%,P=0.03)、合并闭塞性动脉硬化和(或)缺血性脑卒中病史比例(19.7%比0.0%,P=0.0006)均高于对照组。冠状动脉粥样硬化性心脏病组淋巴细胞百分比低于对照组(27.2%±1.2%比31.7%±1.5%,P=0.02),高敏C反应蛋白水平高于对照组[2.0(1.0～4.0)mg/L比1.0(0.5～2.4)mg/L,P=0.02)]。冠状动脉粥样硬化性心脏病组组织蛋白酶抑制素表达水平[1.21(0.98～1.55)比0.97(0.69～1.39),P=0.009)]、α防御素1-3表达水平[0.85(0.58～1.21)比0.61(0.41～0.86),P=0.003)]和α防御素4表达水平[0.78(0.52～1.43)比0.47(0.32～0.74),P=0.001)]均高于对照组。组织蛋白酶抑制素基因表达水平同嗜碱性粒细胞分类水平相关(rs=0.19,P=0.04)。结论稳定型劳力性心绞痛患者外周血单个核细胞抗菌肽组织蛋白酶抑制素和α防御素1-4基因持续高表达可能与冠状动脉粥样硬化有关。Aim To evaluate expression levels of the 5 kinds of antimicrobial peptide genes,cathelicidin（CAMP）and alpha-defensin 1-4（DEFA1-4）in peripheral blood mononuclear cells（PBMC）.Methods Sixty-one patients with coronary artery disease（CAD）who had stable effort angina pectoris and had ≥50% diameter stenosis in left main coronary artery or at least one major coronary artery were involved in this study.Controls（n=53）were those with chest pain,abnormal ecletronic cadiogram or abnormal echocardiography,but had a smooth coronary angiogram（CAG）.Venous blood was obtained before CAG for RNA isolation and routine blood count.Ten μg/patient of the total RNA were used for individual cDNA preparation.Expression levels of genes in individuals were evaluated by quantitative real-time RT-PCR.Results WBC count and subset counts were not different between CAD and control group,except that relative lymphocyte count in percentage was lower in the former than that in the later（27.2%±1.2% vs 31.7%±1.5%,P=0.02）.Level of CAMP gene expression was higher in CAD than that in the control [1.21（0.98～1.55）vs 0.97（0.69～1.39）,P=0.009）].Expression levels of DEFA 1-3 genes were elevated in CAD than that in the control[0.85（0.58～1.21）vs 0.61（0.41～0.86）,P=0.003）].CAD group also presented higher expression level of DEFA 4 gene than the control group [0.78（0.52～1.43）vs 0.47（0.32～0.74）,P=0.001）].The differences of these gene expression levels were not due to variations of WBC subset counts as judged by correlational analysis（all P〉0.05）.CAD patients had higher hs-CRP level than the controls [2.0（1.0～4.0）mg/L vs 1.0（0.5～2.4）mg/L,P=0.02）].Expression levels of DEFA1-3,DEFA4,CAMP were not correlated with CRP level.Conclusion Expression levels of antimicrobial peptides,alpha-defensins and cathelicidin in PBMC,may be associated with coronary artery atherosclerosis.

关 键 词：抗菌肽 防御素 组织蛋白酶抑制素 动脉粥样硬化 

分 类 号：R5[医药卫生—内科学]