自发性高血压大鼠外周血单核细胞亚群与左室重塑的相关性研究  

Correlation analysis between peripheral blood monocyte subsets and left ventricular remodeling in spontaneously hypertensive rats

作　　者：杨国红[1] 周欣[1] 刘军翔[1] 孙婧[1] 孙海英[1] 赵季红[1] 姜铁民[1] 李玉明[1] YANG Guohong;ZHOU Xin;LIU Junxiang;SUN Jing;SUN Haiying;ZHAO Jihong;JIANG Tiemin;LI Yuming(Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People＇s Armed Police Forces, Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury,Tianjin 300162,China)

机构地区：[1]中国人民武装警察部队后勤学院附属医院心脏中心心血管病研究所天津市心血管重塑与靶器官损伤重点实验室,天津300162

出　　处：《临床心血管病杂志》2018年第5期513-518,共6页Journal of Clinical Cardiology

基　　金：国家自然科学基金(No:81600328);天津市自然科学基金(No:16JCQNJC11800);武警后勤学院中心实验室开放基金(No:2015ZXKF11);武警后勤学院附属医院种子基金(No:FYM201533)

摘　　要：目的:探讨自发性高血压大鼠(SHR)外周血单核细胞亚群与高盐加速诱导的高血压性左室重塑的相关性。方法:7周龄雄性SHR按饮食中的NaCl浓度随机分为低盐(LS)组(0.5%NaCl)和高盐(HS)组(8%NaCl),干预12周。所有大鼠以标准的尾压法测定无创尾压,并于处死前进行心脏超声测定;分别在饮食干预前及处死前采取外周血,利用流式细胞术分析单核细胞亚群的变化;以苦味酸-天狼星红(PSR)染色观察心肌组织纤维化程度;以麦芽胚凝集素(WGA)荧光染色计算心肌细胞横截面积(CSA);采用CD68免疫组织化学染色观察心肌间质巨噬细胞的浸润程度;并对所测指标与单核细胞亚群比例进行相关性分析。结果:饮食干预结束时,HS组收缩压、心率、左室质量(LVM)及左室质量指数(LVMI)均显著高于LS组,体质量明显减轻,差异有统计学意义(P<0.05);与LS组比较,HS组在高盐干预12周时CD43^(++)单核细胞比例明显增加,CD43+单核细胞比例明显减低(P<0.05),HS组组内比较也得出同样结果;心脏超声结果显示,HS组左室舒张末期内径(LVEDD)及左室舒张末期容积(LVEDV)显著高于LS组(P<0.05),而反映心脏功能的指标无明显差异;同时,HS组心肌间质及血管周纤维化程度明显增加,CSA显著高于LS组,巨噬细胞浸润程度也明显加重;相关性分析结果显示,高盐干预12周时CD43^(++)单核细胞比例与收缩压、LVM、LVMI、LVEDD、LVEDV、心肌纤维化程度、CSA及巨噬细胞浸润程度均呈正相关关系。结论:高盐干预12周时CD43^(++)单核细胞比例明显增加,其与SHR的左室重塑相关,说明CD43^(++)单核细胞亚群在此病理过程中扮演着重要角色,这一发现为将来以单核细胞为靶点的干预研究指明了方向。Objective：To explore the relationship between peripheral blood monocyte（PBM）subsets and left ventricular remodeling in spontaneously hypertensive rats（SHR）.Method：Seven-week-old male SHR were randomized to receive 0.5% NaCl（low salt,LS）and 8% NaCl（high salt,HS）for 12 weeks.Blood pressure was measured by tail cuff method.Peripheral blood were collected for flow cytometry analysis at baseline and after 12-week salt intervention.At the end of intervention,all rats were anesthetized for echocardiography measurements and then sacrificed.Morphologic staining（collagen deposition,cardiomyocyte hypertrophy and macrophage infiltration）were performed at time of sacrifice.And the relationship between PBM subsets and（LV）remodeling were analyzed at last.Result：Compared with LS group,the systolic blood pressure（SBP）,heart rates（HR）,left ventricular mass（LVM）and LVM index（LVMI）of HS group were significantly increased while body mass（BM）was markedly decreased at the end of 12-week intervention（P〈0.05）.Flow cytometry analysis showed that the percentage of CD43^＋＋ monocyte in HS group were apparently increased while a reduction of CD43＋monocytes were observed compared with LS group（P〈0.05）.Echocardiography measurements demonstrated that the LV end-diastolic dimension（LVEDD）and LV end-diastolic volume（LVEDV）were significantly increased（P〈0.05）though no markedly differences of left ventricular function indexes were found.Moreover,morphologic staining found that a severe myocardial fibrosis,cardiomyocyte hypertrophy and macrophage infiltration were observed in the HS group.And a positive correlation between the percentage of CD43^＋＋ monocyte and SBP,LVM,LVMI,LVEDD,LVEDV,myocardial fibrosis,cardiomyocyte hypertrophy and mocrophage infiltration were also observed.Conclusion：The present study demonstrates a positive correlation between the CD43^＋＋monocytes and left ventricular remodeling which indicates a important role of CD43^＋＋monocyte in t

关 键 词：高盐 高血压 左室重塑 单核细胞亚群 流式细胞术 

分 类 号：R544.1[医药卫生—心血管疾病]