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中华危重症医学杂志(电子版)

中华危重症医学杂志(电子版) ›› 2017, Vol. 10 ›› Issue (05) : 296 -302. doi: 10.3877/cma.j.issn.1674-6880.2017.05.002

所属专题： 文献；

论著

急性心肌梗死患者冠状动脉巨噬细胞M1/M2和硫氧还蛋白水平的相关分析
陈文智1, 赵中1, 张森2, 黄影兰1, 马中富3,†()   
  1. 1. 527200　广东罗定，罗定市人民医院急诊科
    2. 527200　广东罗定，罗定市人民医院老年医学
    3. 510080　广州，中山大学附属第一医院普内科
  • 收稿日期:2017-01-20 出版日期:2017-10-01
  • 通信作者: 马中富
  • 基金资助:
    广东省医学科学技术研究基金项目(A2013898)

Correlation analysis between macrophage M1/M2 proportion and thioredoxin change on coronary artery in patients with acute myocardial infarction

Wenzhi Chen1, Zhong Zhao1, Sen Zhang2, Yinglan Huang1, Zhongfu Ma3,†()   

  1. 1. Department of Emergency Center, the People's Hospital of Luoding, Luoding 527200, China
    2. Department of Geriatric Medicine, the People's Hospital of Luoding, Luoding 527200, China
    3. Department of General Internal Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
  • Received:2017-01-20 Published:2017-10-01
  • Corresponding author: Zhongfu Ma
  • About author:
    Corresponding author: Ma Zhongfu, Email:
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引用本文：

陈文智, 赵中, 张森, 黄影兰, 马中富. 急性心肌梗死患者冠状动脉巨噬细胞M1/M2和硫氧还蛋白水平的相关分析[J]. 中华危重症医学杂志(电子版), 2017, 10(05): 296-302.

Wenzhi Chen, Zhong Zhao, Sen Zhang, Yinglan Huang, Zhongfu Ma. Correlation analysis between macrophage M1/M2 proportion and thioredoxin change on coronary artery in patients with acute myocardial infarction[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2017, 10(05): 296-302.

目的

探讨急性心肌梗死患者巨噬细胞M1/M2亚型比例和硫氧还蛋白（TRX）水平改变及其之间的相关性。

方法

以来源于罗定市人民医院诊断为急性心肌梗死（AMI）患者100例作为观察组，同期选择健康体检者50例为对照组。检测所有患者血清TRX水平并采用流式细胞仪计算M1/M2亚型。另从中山大学法医系收集死亡者冠状动脉前降支标本分为AMI组（21例）及非冠状动脉粥样硬化性心脏病（CAD）组（20例）。计算所有标本巨噬细胞M1/M2亚型比例，并分别采用免疫组织化学法、实时定量核酸扩增（qPCR）及蛋白质印迹法（Western-blotting）检测冠状动脉组织TRX水平。AMI患者及AMI标本冠状动脉M1/M2亚型比例和TRX水平的相关性采用Pearson相关分析，并进行简单线性回归模型进行分析。

结果

与对照组比较，观察组患者血浆中M1/M2亚型比例较对照组显著降低[（7.8 ± 1.3）vs.（3.1 ± 0.9），t = 13.672，P < 0.001]，TRX水平显著升高[（100 ± 22）μg/L vs.（372 ± 17）μg/L，t = 23.654，P < 0.001]。且AMI患者M1/M2亚型比例与TRX水平呈显著负相关（r = -0.611，P < 0.001），回归方程为TRX = -13.654 × M1/M2 + 414.266（R2 = 0.549，P < 0.001）。与非CAD组比较，AMI组冠状动脉组织巨噬细胞M1/M2亚型比例显著下降[（5.56 ± 0.44）vs.（2.77 ± 0.14），t = 10.422，P = 0.005]。AMI组TRX表达在免疫组织化学法（t = 13.537，P < 0.001）、qPCR（t = 14.111，P < 0.001）及Western-blotting（t = 6.153，P < 0.001）检测下均显著高于非CAD组患者。M1/M2亚型比例与TRX水平在免疫组织化学法检测下（r = -0.864，P < 0.001）、qPCR检测（r = -0.856，P < 0.001）、Western-blotting检测（r = -0.868，P < 0.001）均呈显著负相关。回归方程分别为TRX（免疫组织化学法）= -1.174 × M1/M2 + 8.992（R2 = 0.829，P < 0.001）；TRX（qPCR）= -1.214 × M1/M2 + 9.418（R2 = 0.814，P < 0.001）；TRX（Western-blotting）= -0.969 × M1/M2 + 7.392（R2 = 0.837，P < 0.001）。

结论

M1/M2亚型比例与TRX可能共同参与了动脉粥样硬化的形成过程，且急性心肌梗死患者巨噬细胞M1/M2亚型比例与TRX水平呈负相关。

关键词: 急性心肌梗死, 巨噬细胞, 硫氧还蛋白类, 冠状动脉
Objective

To investigate the relationship between the macrophage M1/M2 proportion and thioredoxin (TRX) levels in the plasma of patients with acute myocardial infarction(AMI) and the coronary tissues of the dead.

Methods

A total of 100 patients with acute myocardial infarction from Luoding People's Hospital were collected as the observation group, and 50 healthy people as the control group at the same time. The TRX levels were compared between the two groups, and the macrophage M1/M2 proportion was calculated by flow cytometer. Simultaneously, 21 coronary artery specimens of AMI patients were collected from forensic department of Sun Yat-sen University as the AMI group, and 20 coronary artery specimens of patients without coronary atherosclerotic heart disease (CAD) were collected as the non-CAD group. The macrophage M1/M2 proportion was calculated, and TRX levels were detected by immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) and Western-blotting in the specimens respectively. Pearson analysis and simple linear regression were used to study the correlation between M1/M2 proportion and TRX levels.

Results

Compared with the control group, the M1/M2 proportion was much lower [(7.8 ± 1.3) vs. (3.1 ± 0.9), t = 13.672, P < 0.001], and the TRX levels were much higher [(100 ± 22) μg/L vs. (372 ± 17) μg/L, t = 23.654, P < 0.001] in the observation group. The M1/M2 proportion was negatively correlated with the levels of TRX (r = -0.611, P < 0.001), and the regression equation was that TRX = -13.654 × M1/M2 + 414.266 (R2 = 0.549, P < 0.001). Meanwhile, the M1/M2 proportion significantly decreased [(5.56 ± 0.44) vs. (2.77 ± 0.14), t = 10.422, P = 0.005], the TRX levels detected by IHC (t = 13.537, P < 0.001), qPCR (t = 14.111, P < 0.001) and Western-blotting (t = 6.153, P < 0.001) all remarkedly increased in the AMI group as compared with the non-CAD group. And the M1/M2 proportion was negatively correlated with the TRX levels by IHC (r = -0.864, P < 0.001), qPCR (r = -0.856, P < 0.001) and Western-blotting (r = -0.868, P < 0.001). The regression equations respectively were that TRX (IHC) = -1.174 × M1/M2 + 8.992 (R2 = 0.829, P < 0.001), TRX (qPCR) = -1.214 × M1/M2 + 9.418 (R2 = 0.814, P < 0.001), and TRX (Western-blotting) = -0.969 × M1/M2 + 7.392 (R2 = 0.837, P < 0.001).

Conclusion

M1/M2 proportion and TRX levels may be involved in the formation of atherosclerosis, and the M1/M2 proportion is negatively correlated with the TRX levels.

Key words: Acute myocardial infarction, Macrophages, Thioredoxins, Coronary artery
图1 AMI及非CAD死亡患者冠状动脉中粥样硬化斑块的病理染色图。AMI：急性心肌梗死（acute myocardial infarction）；CAD：冠状动脉粥样硬化性心脏病（coronary atherosclerosis heart disease）；注：a图为AMI组，显示冠状动脉纵断面内膜不光滑，见吞噬脂质的泡沫样细胞，斑块形成；b图为非CAD组，显示冠状动脉结构正常（HE染色　×400）
图2 qPCR检测两组冠状动脉组织标本中TRX的表达情况。注：qPCR：实时定量核酸扩增（quantitative polymerase chain reaction）；TRX：硫氧还蛋白（thioredoxin）；CAD：冠状动脉粥样硬化性心脏病（coronary atherosclerosis heart disease）；AMI：急性心肌梗死（acute myocardial infarction）；与非CAD组比较，*P < 0.05
图3 Western-blotting检测两组冠状动脉组织标本中TRX的表达情况。注：TRX：硫氧还蛋白（thioredoxin）；CAD：冠状动脉粥样硬化性心脏病（coronary atherosclerosis heart disease）；AMI：急性心肌梗死（acute myocardial infarction）；GAPDH：3-磷酸甘油醛脱氢酶（glyceraldehyde 3-phosphate dehydrogenase）；与非CAD组比较，*P < 0.05
表1 免疫组织化学法检测AMI组及非CAD组死亡者M1/M2亚型比例和TRX表达水平的比较（ ± s）
组别 例数 M1/M2 TRX
AMI组 30 2.77 ± 0.14 5.2 ± 1.4
非CAD组 20 5.56 ± 0.44 1.0 ± 0.0
t值 ? 10.422 13.537
P值 ? 0.005 < 0.001
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