急性冠脉综合征病程中MDSCs的动员及作用研究-东南大学学报医学版

急性冠脉综合征病程中MDSCs的动员及作用研究

单位：1. 东南大学附属中大医院心内科, 江苏南京 210009;
2. 上海交通大学附属新华医院心内科, 上海 200092

分类号：R541.4

出版年·卷·期（页码）：2012·31·第三期（254-260）

摘要：

目的:研究急性冠脉综合征(ACS)时体内髓系抑制细胞(MDSCs)CD11b⁺Gr-1⁺的动态变化过程以及MDSCs参与ACS过程的可能机制。方法:55例患者根据临床症状及冠脉造影情况分为ACS组(n＝42)和对照组(n＝13),流式细胞术分析外周血中MDSCs比例(MDSCs%)。24只BLAB/C小白鼠随机分为普通饮食组(n=12)和高脂饮食组(n=12),分别喂养8周,流式细胞术分析外周血中MDSCs%,全自动生化分析仪测定血清中总胆固醇、低密度脂蛋白水平,HE染色及免疫荧光分析动脉斑块的性质、特点。30只雄性BLAB/C小白鼠随机分为对照组(n=10)和急性心肌梗死(AMI)模型组(n=20),流式细胞术分析骨髓、脾脏、外周血中MDSCs%;分离培养小鼠骨髓单个核细胞,以粒细胞-巨噬细胞集落刺激因子(GM-CSF)诱导分化48 h,加入100 mg·L^-1氧化修饰低密度脂蛋白(ox-LDL)孵育48 h,以油红O染色鉴定泡沫细胞。结果:与对照组相比ACS患者外周血中MDSCs%显著升高(P<0.001),ACS患者经冠脉介入治疗(PCI)后外周血中MDSCs%进行性降低;经高脂饮食喂养8周后小鼠外周血中MDSCs%显著升高(P<0.001),且以CD11b⁺Ly6G⁺粒系亚型为主,CD11b⁺Ly6C⁺单核系亚型可吞噬脂质形成单核样泡沫细胞参与不稳定斑块的形成;小鼠AMI超急性期至急性期MDSCs在体内呈现动态动员变化,与肌钙蛋白呈现较好相关性(P<0.001)。结论:CD11b⁺Ly6C⁺MDSCs可逐步分化成为泡沫样细胞,参与动脉不稳定斑块的进展,形成ACS的积累阶段;CD11b⁺Ly6G⁺MDSCs可分化为中性粒样细胞,参与形成ACS的急性病程进展;MDSCs持续参与ACS的发病过程,MDSCs%测定可为AMI发生发展的诊断提供参考。

Objective: To study the dynamic process of CD11b⁺Gr-1⁺myeloid derived suppressor cells (MDSCs) in ACS and analyze the possible mechanisms of MDSCs involved in ACS. Methods: 55 patients were divided into ACS(n=42) and control group(n=13) according to clinical symptoms and coronary angiography; 24 BLAB/C mice randomly divided into normal diet group(n=12) and high fat diet group(n=12) for 8 weeks; 30 male BLAB/C mice were randomly divided into control group(n=10) and acute myocardial infarction(AMI) group(n=20); percentage of MDSCs(MDSCs%) in bone marrow, spleen, peripheral blood were analyzed by flow cytometry; automatic biochemical analyzer were used to detect TC, LDL levels in serum; HE staining and immunofluorescence were used to identify the nature of arterial plaque and characteristics; MDSCs were cultured and GM-CSF were added to induce the differentiation of the cells for 48 hours followed by adding oxidized low density lipoprotein(ox-LDL 100 mg·L^-1) for another 48 hours and foam cell were stained by oil red O. Results: Compared with the control group MDSCs in ACS patients was significantly higher(P<0.001) and MDSCs% in peripheral blood decreased greatly after PCI; 8 weeks of high-fat diet feeding significantly elevated CD11b⁺Ly6G⁺MDSCs% in peripheral blood(P<0.001),CD11b⁺Ly6C⁺MDSCs phagocytized lipids and developed into monocyte-like foam cells involved in the formation of unstable plaques; mobilization of MDSC% in AMI mice showed dynamic changes from hyperacute to acute phase as well as good correlation with troponin I(P<0.001). Conclusion: CD11b⁺Ly6C⁺MDSCs can gradually differentiate into foam-like cells involved in the progress of arterial instability plaque at the accumulating phase of ACS; CD11b⁺Ly6G⁺ MDSCs can differentiate into neutrophil-like cells involved in the progression of acute phase of ACS; MDSCs are involved in all pathogenesis process of ACS and can provide a reference for the diagnosis of AMI.

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