巨噬细胞迁移抑制因子及炎症因子在昼夜节律改变小鼠心脏缺血再灌注损伤中的作用  

Down-regulated MIF aggravates cardiac ischemia/reperfusion injury in mice with circadian disturbance

作　　者：王璐萍 陶潞渊 黄凯宇[2] 宋喜发 张素勤[2] 殷日鹏[2] WANG Luping;TAO Luyuan;HUANG Kaiyu(Department of Endocrinology,Fourth Affiliated Hospital of Z.hejiang University School of Medicine,Yiwu 322000,China)

机构地区：[1]浙江大学附属第四医院内分泌科,义乌322000 [2]温州医科大学附属第二医院心内科

出　　处：《浙江医学》2018年第11期1170-1174,1182,共6页Zhejiang Medical Journal

基　　金：浙江省自然科学基金项目(LY13H020004);温州市科技局项目(Y20130167;Y20130211)

摘　　要：目的研究巨噬细胞迁移抑制因子(MIF)及炎症因子在昼夜节律改变小鼠心脏缺血再灌注损伤中的作用。方法 36只小鼠在12h/12h昼夜交替和持续黑暗环境下饲养2周,分为Normal组、Normal缺血再灌注组、Disrupted组、Disrupted缺血再灌注组,每组9只,4周后完成造模,Normal组和Disrupted组行心超检测、心肌病理检查、心肌MIF、IL-6、TNF-α、IL-8检测。另对Normal缺血再灌注组及Disrupted缺血再灌注组行心脏缺血再灌注处理,处理后分别检测心肌IL-6、TNF-α、IL-8等炎症因子表达,心肌组织局部炎症浸润程度及超声心动图。结果 Disrupted组小鼠心肌MIF表达较Normal组显著下降(P<0.05)。Disrupted缺血再灌注组和Normal缺血再灌注组相比,心脏IL-6、TNF-α、IL-8表达显著增高,病理检查示心肌局部炎症浸润增加,心超示心功能受损加重(均P<0.05)。结论改变小鼠昼夜节律致心肌MIF蛋白表达下降,心肌缺血再灌注后炎症因子IL-6、TNF-α、IL-8表达增加,局部炎症反应加重,心功能恶化。Objective To examine the effect of macrophage migration inhibitory factor（MIF） and inflammatory factors on cardiac ischemia/reperfusion（I/R） injury in mice with disturbed circadian rhythm. Methods Thirty six mice were randomly housed in 12 h light/dark cycle（normal） or constant darkness（disrupted） environment, and equally divided into normal group, normal I/R group, disrupted group and disrupted I/R group. After 4 weeks, the heart function, myocardial HE staining, myocardial MIF protein and the inflammatory cytokines were detected in normal group and disrupted group. The cardiac ischemia reperfusion injury was induced in normal I/R group and disrupted I/R group, respectively. Then the expression of inflammatory cytokines s IL-6, TNF-α and IL-8, the degree of local inflammatory infiltration and the heart function were examined. Results WB revealed that cardiac MIF expression was significantly lower in the disrupted group than that in the normal group. Following ischemia and reperfusion, mice in the disrupted I/R group had more serious cardiac inflammatory response and lower heart function index than the normal I/R group（P〈0.05）; the cardiac expression of IL-6, TNF-α and IL-8 was higher than that of normal I/R group（P〈0.05）. Conclusion Disturbing the circadian rhythm of mice by constant dark environment can lead to the lower expression of MIF and higher expression of inflammatory factors after cardiac ischemia/reperfusion injury, indicating that down-regulated MIF may be associated with aggravation of local inflammatory and worse cardiac function.

关 键 词：黑暗环境 昼夜节律 缺血再灌注损伤 MIF IL-6 TNF-α IL-8 

分 类 号：R54[医药卫生—心血管疾病]