冠心病患者巨噬细胞移动抑制因子水平增高及其与ADMA-NO的关系  

Elevated levels of macrophage migration inhibitory factor in coronary artery disease is correlated with ADMA-NO

作　　者：骆骅[1,2] 周志凌[2] 刘媛[2] 姚轻舟[1,2] 钟诗龙[2] 林秋雄[2] 单志新[2] 杨敏[2] 朱杰宁[2] 邓春玉[2] 雷和平[2] 余细勇[1,2] 

机构地区：[1]南方医科大学药学院,广东广州510515 [2]广东省人民医院(广东省医学科学院)医学研究中心,广东广州510080

出　　处：《热带医学杂志》2013年第3期278-281,287,F0004,共6页Journal of Tropical Medicine

基　　金：国家自然科学基金(81070103;81202602);国家973计划(2012CB526602);广东省中医药局课题(20111112)

摘　　要：目的检测冠心病患者血浆巨噬细胞移动抑制因子(MIF)含量以及探讨MIF在促内皮功能紊乱中的相关病理生理机制。方法将173例冠心病患者分为3个亚组:确诊为冠心病但未接受经皮冠状动脉介入治疗(PCI)的病人(n=33)、刚接受PCI术的病人(7d内)(n=43)、接受PCI术大于6个月的病人(n=97),另选62名健康体检者作为健康对照组。采用ELISA检测血浆MIF含量,qRT-PCR检测外周血白细胞中MIF、CD74mRNA水平。同时以Eahy926细胞为研究对象,采用MIF刺激,观察相关炎性因子的表达及活性氧(ROS)、NO水平。结果冠心病人和健康人群MIF的含量分别为(1422±53.01)pg/ml、(1103±64.52)pg/ml(P<0.01)。冠心病人群MIF的含量比健康人群显著上升,其接受PCI术后的时间长短与MIF含量无显著关系,但随着时间的延长其MIF的含量有降低趋势。外周血白细胞中MIF、CD74mRNA含量与健康对照组相比有上升趋势,但差异无统计学意义(P>0.05)。培养细胞中加入20ng/mlMIF时,炎性因子表达增高,二甲基精氨酸二甲胺水解酶2(DDAH2)mRNA量下降显著,ROS增多,NO量下降。结论血浆MIF的升高可能是冠心病的一个危险因素,同时MIF可能通过MIF-ROS-DDAH2-ADMA-NO途径,导致血管内皮功能紊乱,促进动脉粥样硬化的发生与发展。Objective To evaluate the expression of circulating macrophage migration inhibitory factor （MIF） in patients with coronary artery disease （CAD） and to explore the pathophysiological role of MIF in endothelial dysfunction. Methods The levels of plasma MIF in 173 patients with CAD and 62 healthy subjects, after overnight fasting, were measured by ELISA. The levels of MIF and CD74 mRNA from peripheral white blood cells were detected by qRT-PCR. CAD patients were divided into 3 groups according to the duration after percutaneous transluminal coronary intervention （PCI）. The effect of MIF stimulation on the expression of ROS and NO was studied using Eahy 926 endothelial cells. Results In CAD patients, the concentration of MIF in plasma （1 422_＋53.01）pg/ml was higher than the healthy subjects, （1 103_＋64.52） pg/ml （P〈0.01）. The levels of certain inflammatory markers （e.g. TF, MMP-1, ET-1） and ROS were also increased in cells treated with MIF （20 ng/ml）. However, the levels of dimethylargine dimethylaminohydrolase 2 （DDAH2） mRNA and NO were decreased. Conclusion High level of MIF is a risk factor for CAD patients. The MIF-ROS-DDAH2-ADMA-NO signaling pathway may be involved in endothelial dysfunction and also the progression of coronary artery disease.

关 键 词：巨噬细胞移动抑制因子 非对称性二甲基精氨酸 冠心病 

分 类 号：R541.4[医药卫生—心血管疾病]