Correlation analysis between peripheral blood monocyte subsets and left ventricular remodeling in spontaneously hypertensive rats
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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。Abstract: 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 this process and prompts a valuable therapy target for further study.
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Key words:
- high salt /
- hypertension /
- left ventricular remodeling /
- monocyte subset /
- flow cytometry
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[1] Benjamin EJ,Blaha MJ,Chiuve SE,et al.Heart Disease and Stroke Statistics-2017 Update:A Report From the American Heart Association[J].Circulation,2017,135(10):e146-e603.
[2] 陈伟伟,高润霖,刘力生,等.《中国心血管病报告2015》概要[J].中国循环杂志,2016,31(6):521-528.
[3] Adrogué HJ,Madias NE.Sodium and potassium in the pathogenesis of hypertension:focus on the brain[J].Curr Opin Nephrol Hypertens,2017,26(2):106-113.
[4] Sawant SH,Bodhankar SL.Flax lignan concentrate reverses alterations in blood pressure,left ventricular functions,lipid profile and antioxidant status in DOCA-salt induced renal hypertension in rats[J].Ren Fail,2016,38(3):411-423.
[5] Ling YH,Krishnan SM,Chan CT,et al.Anakinra reduces blood pressure and renal fibrosis in one kidney/DOCA/salt-inducedhypertension[J].Pharmacol Res,2017,116:77-86.
[6] Heine GH,Ortiz A,Massy ZA,et al.Monocyte subpopulations and cardiovascular risk in chronic kidney disease[J].Nat Rev Nephrol,2012,8(6):362-369.
[7] 杨国红,卢芮伊,孙海英,等.四色流式分析冠心病患者外周血单核细胞亚群及单核细胞-血小板聚集体的变化[J].临床心血管病杂志,2013,29(1):29-33.
[8] 周颖,汪小君,罗燕薇,等.循环单核细胞亚群联合肾功能对急性ST段抬高心肌梗死患者预后危险分层的评估[J].临床心血管病杂志,2017,33(6):534-539.
[9] Yang GH,Zhou X,Ji WJ,et al.Overexpression of VEGF-C attenuates chronic high salt intake-induced left ventricularmaladaptive remodeling in spontaneously hypertensive rats[J].Am J Physiol Heart Circ Physiol,2014,306(4):H598-609.
[10] 卢芮伊,周欣,姬文婕,等.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[J].细胞与分子免疫学杂志,2014,30(2):131-134.
[11] Zhou X,Zhang L,Ji WJ,et al.Variation in dietary salt intake induces coordinated dynamics of monocyte subsets and monocyte-platelet aggregates in humans:implications in end organ inflammation[J].PloS one,2013,8(4):e60332.
[12] Krychtiuk KA,Lenz M,Koller L,et al.Monocyte subset distribution is associated with mortality in critically ill patients[J].Thromb Haemost,2016,116(5):949-957.
[13] Larson SR,Atif SM,Gibbings SL,et al.Ly6C(+) monocyte efferocytosis and cross-presentation of cell-associated antigens[J].Cell Death Differ,2016,23(6):997-1003.
[14] Szelényi Z,Fazakas?,Szénási G,et al.Inflammation and oxidative stress caused by nitric oxide synthase uncoupling might lead to leftventricular diastolic and systolic dysfunction in patients with hypertension[J].J Geriatr Cardiol,2015,12(1):1-10.
[15] Xu Y,Chen Y,Li D,et al.Hypertension,fluid overload and micro inflammation are associated with left ventricular hypertrophy in maintenance hemodialysis patients[J].Ren Fail,2013,35(9):1204-1209.
[16] Celik T,Fici F.The association between inflammation and left ventricular diastolic dysfunction in patients with hypertension:another piece of the puzzle[J].Nutr Metab Cardiovasc Dis,2013,23(6):e26-27.
[17] Gao F,Han ZQ,Zhou X,et al.High salt intake accelerated cardiac remodeling in spontaneously hypertensive rats:time window of left ventricular functional transition and its relation to salt-loading doses[J].Clin Exp Hypertens,2011,33(7):492-499.
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