切换至 "中华医学电子期刊资源库"
高级检索
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:
全文 ( ) 下载PDF ( ) 导出引用
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/OL]. 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/OL]. 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
1
中国医师协会急诊医师分会，中华医学会心血管病学分会，中华医学会检验医学分会. 急性冠脉综合征急诊快速诊疗指南[J/CD]. 中华危重症医学杂志（电子版），2016，9(2):73-80.
2
安豫，党海燕，安泉. 巨噬细胞功能与动脉粥样硬化研究进展[J]. 医学综述，2016，22(14):2727-2730.
3
郭明，张宗辉，杨杰. 非ST段抬高急性冠脉综合征患者血清超敏C反应蛋白水平与GRACE危险评分的相关性研究[J/CD]. 中华危重症医学杂志（电子版），2013，6(2):86-89.
4
李广平. C反应蛋白与冠状动脉疾病关系的研究进展[J]. 天津医药，2009，37(11):985-987.
5
白瑞娜，郗瑞席，冯志博，等. 巨噬细胞与动脉粥样硬化—亚型及功能[J]. 中国循环杂志，2014，29(5):393-395.
6
Quercioli A, Mach F, Montecucco F. Inflammation accelerates atherosclerotic processes in obstructive sleep apnea syndrome (OSAS)[J]. Sleep Breath, 2010, 14 (3): 261-269.
7
McPherson R, Davies RW. Inflammation and coronary artery disease: insights from genetic studies[J]. Can J Cardiol, 2012, 28 (6): 662-666.
8
Vieira Potter VJ, Strissel KJ, Xie C, et al. Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity[J]. Endocrinology, 2012, 153 (9): 4266-4277.
9
许媛媛，李世英. 单核细胞趋化蛋白-1与动脉粥样硬化及缺血性脑血管病的研究进展[J]. 临床神经病学杂志，2012，25(3):239-240.
10
徐志鹏，左国平，靳建亮. 巨噬细胞异质性及其在炎症调控中的研究进展[J]. 细胞与分子免疫学杂志，2015，31(12):1711-1714.
11
阮静瑶，陈必成，张喜乐，等. 巨噬细胞M1/M2极化的信号通路研究进展[J]. 免疫学杂志，2015(10):911-917.
12
应航洁，史丽云. 巨噬细胞极性转化及其分子调控机制[J]. 医学综述，2014，20(17):3095-3097.
13
Liu YC, Zou XB, Chai YF, et al. Macrophage polarization in inflammatory diseases[J]. Int J Biol Sci, 2014, 10 (5): 520-529.
14
Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation[J]. Nat Rev Immunol, 2008, 8 (12): 958-969.
15
Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions[J]. Immunity, 2010, 32 (5): 593-604.
16
Meyer Y, Buchanan BB, Vignols F, et al. Thioredoxins and glutaredoxins: unifying elements in redox biology[J]. Angiology, 2009, 60 (4): 419-426.
17
Sato A, Hara T, Nakamura H, et al. Thioredoxin-1 suppresses systemic inflammatory responses against cigarette smoking[J]. Antioxid Redox Signal, 2006, 8 (9-10): 1891-1896.
18
Spindel ON, Yan C, Berk BC. Thioredoxin-interacting protein mediates nuclear-to-plasma membrane communication: role in vascular endothelial growth factor 2 signaling[J]. Arterioscler Thromb Vasc Biol, 2012, 32 (5): 1264-1270.
19
Shioji K, Nakamura H. Thioredoxin and atherosclerosis[J]. Rinsho Byori, 2003, 51 (11): 1106-1110.
20
Madrigal-Matute J, Fernandez-Garcia CE, Blanco-Colio LM, et al. Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis[J]. Free Radic Biol Med, 2015 (86): 352-361.
21
Rajappa M, Sen SK, Sharma A. Role of pro-/anti-inflammatory cytokines and their correlation with established risk factors in south indians with coronary artery disease[J]. Angiology, 2009, 60 (4): 419-426.
22
El Hadri K, Mahmood DF, Couchie D, et al. Thioredoxin-1 promotes anti-inflammatory macrophages of the m2 phenotype and antagonizes atherosclerosis[J]. Arterioscler Thromb Vasc Biol, 2012, 32 (6): 1445-1452.
[1] 张凯, 乔永杰, 林志强, 刘健, 邓泽群, 谭飞, 曾健康, 李嘉欢, 李培杰, 周胜虎. 假体周围骨溶解中巨噬细胞极化的机制研究进展[J/OL]. 中华关节外科杂志(电子版), 2024, 18(05): 618-625.
[2] 杨瑾, 刘雪克, 张媛媛, 金钧, 韦瑶. 肠道微生物来源石胆酸对脓毒症相关肝损伤的保护作用[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(04): 265-274.
[3] 王友芳, 李兴超, 刘清敏, 刘德彬, 刘松伍, 郭冬冬, 车峰远. 应激性高血糖指数对经皮冠状动脉介入术后急性心肌梗死患者发生主要不良心脑血管事件的预测价值[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(02): 124-129.
[4] 顾盼盼, 董传莉, 宋梦瑶, 瞿色华, 杨小迪, 周瑞. 不完全性川崎病患儿临床特征及冠状动脉损害情况分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(04): 446-451.
[5] 李卓骋, 陈羽翔, 高亮, 张宇, 朱许源, 马晓杰, 李涛, 赵甜甜, 蒋鸿涛. 巨噬细胞-肌成纤维细胞转化在肾纤维化过程中的作用[J/OL]. 中华移植杂志(电子版), 2024, 18(03): 181-185.
[6] 朱军, 宋家伟, 乔一桓, 郭雅婕, 刘帅, 姜玉, 李纪鹏. M2型巨噬细胞特征基因与结肠癌免疫微环境研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 303-311.
[7] 周敏, 徐阳, 胡莹, 黄先凤. 维持性血液透析患者血清β-CTX、N-MID 和PICP 与冠状动脉钙化的关系及其诊断价值[J/OL]. 中华肾病研究电子杂志, 2024, 13(05): 256-260.
[8] 李松栗, 黄蔚, 巢杰, 杨毅, 邱海波. 单核/巨噬细胞来源的细胞外囊泡在急性呼吸窘迫综合征中的研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(03): 253-257.
[9] 牟超鹏, 宗斌, 刘奕, 史美英, 徐杜娟, 冯春光. 经远端桡动脉与经常规桡动脉行急诊冠脉介入诊疗后穿刺部位血肿的对比[J/OL]. 中华临床医师杂志(电子版), 2024, 18(03): 275-282.
[10] 邵天朋, 周英文, 陈延鹏, 宋兆伟. 栓塞治疗合并冠状动脉-支气管动脉瘘咯血患者一例[J/OL]. 中华介入放射学电子杂志, 2024, 12(03): 284-286.
[11] 王文珠, 刘建, 袁常秀, 石亚飞, 尤培军. 竖脊肌平面阻滞对非体外循环冠状动脉旁路移植术中阿片类药物用量的影响[J/OL]. 中华诊断学电子杂志, 2024, 12(03): 155-159.
[12] 黄锦, 温静, 李佳霖, 韩丹, 刘翠华, 杨殿辉, 张洋洋. 双联抗血小板药物对溃疡性结肠炎患者的影响及处理策略[J/OL]. 中华胃肠内镜电子杂志, 2024, 11(03): 195-199.
[13] 王亚芳, 荣素然, 石向欣, 杨晓欧, 许金金, 王敬祥. 切割球囊对老年轻中度冠状动脉钙化病变患者远期预后的影响[J/OL]. 中华老年病研究电子杂志, 2024, 11(03): 19-23.
[14] 郑屹, 刘莹, 张煜坤, 李广平, 陈康寅, 刘彤. 既往及新发心房颤动对急性心肌梗死患者远期卒中风险的影响[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(05): 406-417.
[15] 周洪千, 张煜坤, 顾天舒, 胡苏涛, 姜超, 张雪, 张昊, 陶华岳, 刘行, 刘彤, 陈康寅. 既往出血性脑卒中患者行经皮冠脉介入治疗后不良事件的危险因素分析[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(04): 323-329.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号