单核细胞亚群在大鼠心肌缺血再灌注模型中的动态变化及意义  

Dynamic changes of peripheral blood monocyte subsets after myocardial ischemia /reperfusion in rats

作　　者：卢芮伊[1,2] 周欣[2] 姬文婕[3] 罗悦晨[2] 杨国红[2] 孙海英[2] 葛兰[2] 姜铁民[2] 李玉明[2] 

机构地区：[1]天津医科大学研究生院,天津300070 [2]中国人民武装警察部队后勤学院附属医院武警部队心血管病研究所心脏中心,天津300162 [3]中国人民武装警察部队后勤学院附属医院呼吸与重症医学科,天津300162

出　　处：《细胞与分子免疫学杂志》2014年第2期131-134,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81070121;81170238);天津市自然科学基金(09ZCZDSF04200;11JCYBJC12000)

摘　　要：目的观察单核细胞不同亚群在大鼠心肌缺血再灌注(I/R)模型中的动态变化,并探讨其与I/R损伤后炎症程度及组织修复的关系。方法 Wistar大鼠16只随机分为缺血再灌注组(I/R组)和假手术组(sham组)。采用结扎左冠状动脉前降支45 min后再灌注的方法制备I/R模型。于术前、术后1、3、5、7、14 d抽取大鼠尾静脉血,运用流式细胞术将单核细胞分为CD172a+CD43low和CD172a+CD43high两个亚群,检测各时间点单核细胞亚群的比例,并于术后第30天取心脏行Masson及麦胚凝集素(WGA)染色,观察心肌梗死区纤维化程度及心肌细胞肥大程度与单核细胞表型变化的关系。结果 I/R组CD172a+CD43low单核细胞比例在术后第1天较基线显著升高(P<0.05),第3天达到高峰(P<0.01),之后逐渐下降,从第7天起与基线水平一致;Sham组CD172a+CD43low单核细胞比例在术后第1天升高,与基线相比差异有统计学意义(P<0.05),从第3天起降至基线水平;与sham组相比,I/R组第3天时CD172a+CD43low比例较显著性升高(P<0.01),其余时间点则无显著性差异。两组大鼠CD172a+CD43high细胞比例在各组呈现与CD43low相反的变化。Masson及WGA染色结果显示,I/R组大鼠心肌存在大量胶原纤维的沉积(P<0.05),且心肌细胞存在不同程度的肥大(P<0.01)。术后第3天CD172a+CD43low单核细胞比例与术后30 d左室壁心肌纤维化程度的相关性分析结果显示两者呈正相关(r=0.86,P<0.05)。结论研究表明大鼠心肌I/R后单核细胞亚群发生了动态变化,具有促炎症表型的CD172a+CD43low单核细胞可能成为心肌I/R损伤的治疗靶点。Objective To investigate the dynamic changes of monocyte subsets after myocardial ischemia/repeffusion （I/R） in rats and their correlations with myocardial repair after I/R injury. Methods Sixteen male Wistar rats were randomly divided into two groups： I/R group and sham group. Myocardial I/R was induced by left anterior descending coronary artery ligation for 45 min followed by permanent reperfusion. Peripheral blood was harvested from the tail vein to evaluate the dynamics of CD172a＋ CD43^（low） and CD172a ＋ CD43^（low） monocyte subsets by flow cytometry at baseline and on day 1, 3, 5, 7 and 14 after I/R injury. Survival rats were sacrificed on day 30, and the hearts were prepared for the evaluation of collagen deposition （Masson＇s trichrome staining） and myocardial hypertrophy （wheat-germ aggluUnin staining）. Results In I/R group, there was a significant increase of CD172a＋ CD43^（low） monocytes on day 1 compared with the baseline （ P〈O.05）, followed by an increasing trend, which peaked on day 3 （P〈0.O1）, and then underwent a gradual decreasing trend to the baseline on day 7. In sham group, a similar increasing trend of CD172a ＋ CD43^（low） monocytes was observed on day 1 （ P 〈 0.05 ） compared with the baseline, whereas this trend declined rapidly to the baseline level on day 3. The proportion of CD172a＋ CD43^（low） in I/R group on day 3 was much higher than that in the sham group （P〈0.01）. There were no significant differences betweenthe two groups at any other time points. A reciprocal change of CD172a ＋ CD43high monocytes was observed during investiga- tion. Cardiac pathological evaluation revealed that there was a significant reparative fibrosis in the infarct area （ P 〈 0.05） along with a significant myocardial hypertrophy in non-infarct area （P 〈0.01 ） in I/R group. Correlation analysis showed that the proportion of CD172a ＋ CD43^（low） monocytes on day 3, but not CD172a＋ CD43high monocytes, was positively correlated wi

关 键 词：单核细胞 亚群 缺血再灌注 流式细胞术 

分 类 号：R392.11[医药卫生—免疫学] R541.6[医药卫生—基础医学]