M2巨噬细胞对新生乳鼠受损心脏组织的再生和修复机制  

M2 macrophage promotes myocardial regeneration by modulating nerve regeneration and angiogenesis in neonatal mice

作　　者：王茜 张家坤 刘青 孙琳[3] 李晶洁[3] Wang Qian;Zhang Jiakun;Liu Qing;Sun Lin;Li Jingjie(Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China;Department of Cardiology, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China;Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China)

机构地区：[1]哈尔滨医科大学附属第四医院胸痛中心,哈尔滨150001 [2]天津市宝坻区人民医院心内科,天津301800 [3]哈尔滨医科大学附属第一医院心内科二病房,哈尔滨150001

出　　处：《首都医科大学学报》2022年第2期178-186,共9页Journal of Capital Medical University

基　　金：哈尔滨市科学技术局(2017RAXQJ068)。

摘　　要：目的以受损心脏完全再生的新生乳鼠为模型,探究极化巨噬细胞是否对心肌再生和修复产生影响。方法采用数字表法随机选取新生健康乳鼠并于出生后第1天或第7天行心尖切除术,切除后直接将体外极化的M1或M2型巨噬细胞注射到切除部位,根据是否注射巨噬细胞及细胞类型进行分组。术后7 d处死动物,采用组织学方法评价心肌修复情况、免疫组织化学和分子生物学分析检测相应心肌区域交感神经和血管生成情况。结果与对照组相比,M1巨噬细胞通过加重炎性反应抑制心肌修复。M2巨噬细胞通过减轻炎性反应、刺激交感神经和增强受损心肌组织的血管生成,显著改善心肌再生和修复。M2巨噬细胞植入后,损伤区血管内皮生长因子和神经生长因子浓度均呈剂量依赖性升高。结论M2巨噬细胞在体内可促进心肌的再生和修复,提示调节巨噬细胞极化可能为心脏疾病提供一种新的治疗策略。Objective To determine the effects of polarized macrophages on myocardial regeneration and repair.Methods Macrophages were isolated from rat bone marrow and polarized to M1 or M2 microphage in vitro.Apical resection surgery was performed in neonatal mice on postnatal day 1 or day 7.M1 or M2 macrophages were directly injected into the resection site post resection to determine the effects of two types of polarized macrophages on myocardial regeneration and repair.Animals were sacrificed seven days after surgery to evaluate the myocardial repair with histological methods.Nerve regeneration and angiogenesis were also determined by immunohistochemistry and molecular biology analysis.Results Compared with control animals,M1 macrophage administration inhibited myocardial repair by aggravating inflammatory response.In contrast,M2 macrophage implantation significantly improved myocardial regeneration and repair by alleviating inflammation,stimulating sympathetic innervation and enhancing angiogenesis in damaged myocardial tissue.M2 macrophage implantation also increase the levels of vascular endothelial growth factor(VEGF)and nerve growth factor(NGF),two critical factors for neo-angiogenesis and sympathetic innervation respectively,in damaged area in a dose-dependent manner.Conclusion Our study demonstrates that M2 macrophage promotes myocardial regeneration and repair in vivo,suggesting that modulating macrophage polarization may provide a novel therapeutic strategy to heart disease.

关 键 词：巨噬细胞 心尖切除 心脏再生 

分 类 号：R541[医药卫生—心血管疾病]