中性粒细胞外陷阱与冠心病急性心肌梗死关联的临床流行病学研究

帅梓强; 张成鑫; 安城; 葛圣林

doi:10.16462/j.cnki.zhjbkz.2021.09.021

中性粒细胞外陷阱与冠心病急性心肌梗死关联的临床流行病学研究

doi: 10.16462/j.cnki.zhjbkz.2021.09.021

230022 合肥，安徽医科大学第一附属医院心脏大血管外科

基金项目:

安徽省自然科学基金 1808085MH279

详细信息

通讯作者:
葛圣林，E-mail: geshenglin@ahmu.edu.cn

中图分类号: R181.3⁺2;R654.2
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- 被引次数: 0
出版历程
- 收稿日期: 2021-07-04
- 修回日期: 2021-08-09
- 网络出版日期: 2021-10-23
- 刊出日期: 2021-09-10

Clinical epidemiological study on the association between neutrophil extracellular traps and acute myocardial infarction among coronary atherosclerotic heart disease

Department of Cardiovascular Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China

Funds:

Natural Foundation of Anhui Province 1808085MH279

More Information

Corresponding author: GE Sheng-lin, E-mail: geshenglin@ahmu.edu.cn

摘要

摘要: 目的探讨冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease, CAHD)急性心肌梗死(acute myocardial infarction, AMI)发作及冠脉旁路移植术(coronary artery bypass graft, CABG)后周围血中性粒细胞胞外陷阱(neutrophil extracellular traps, NETs)水平变化及作用，为有效防控CAHD及AMI提供新依据。方法选择AMI患者和健康对照(healthy control, HC)各52例，ELISA法检测AMI发病时治疗前(pre-treatment, PRT)组及手术治疗后(post-operative treatment, POT)组周围血NETs、B因子活化片段a(fragment a of the factor B, Ba)、补体片段5a(fragment a of the 5th complement, C5a)及髓过氧化酶(myeloperoxidase, MPO)水平，检测结果的组间比较采用t检验，PRT组内观察指标间的相关性分析采用Pearson相关分析。结果 PRT组和POT组各检测指标均高于HC组，PRT组心肌肌钙蛋白I(cardiac troponin I, cTnI)、NETs、Ba、C5a和MPO高于POT组[分别为(0.279±0.132)ng/ml vs.(0.016±0.008)ng/ml, P < 0.001；(0.466±0.143)OD值vs.(0.378±0.151)OD值, P=0.002；(72.812±30.144)pg/ml vs.(60.491±28.323)pg/ml, P=0.001；(327.112±203.228)ng/ml vs.(260.411±135.984)ng/ml, P=0.025；(75.782±33.596)ng/ml vs.(58.462±29.647)ng/ml, P=0.008]；PRT组中NETs分别与Ba、C5a及MPO呈正相关(分别为r=0.394, P=0.001；r=0.324, P=0.030和r=0.406, P < 0.001)，且Ba与C5a呈正相关(r=0.436, P < 0.001)，但cTnI仅与NETs呈正相关(r=0.352, P=0.008)。POT组中，cTnI虽已恢复正常值范围，但仍高于HC组cTnI [(0.016±0.008)pg/ml vs.(0.012±0.007)pg/ml, P=0.016]。结论 CAHD患者在AMI发作期和接受CABG手术后，持续存在高水平NETs及与其相关的高补体旁路活化状态，有助于病情进展和心肌梗死再发，干预NETs形成可能是防治CHAD进展和AMI发生的潜在途径之一。
- 冠状动脉粥样硬化性心脏病 /
- 急性心肌梗死 /
- 冠脉旁路移植术 /
- 中性粒细胞胞外陷阱 /
- 发病机制
Abstract: Objective To investigate the change and its roles of neutrophil extracellular traps (NETs) in peripheral blood from patients with coronary atherosclerotic heart disease (CAHD) during their acute myocardial infarction (AMI) and post operation of coronary artery bypass graft (CABG), and to proride effective prevention and control of CAHD and AMI. Methods A total of 52 patients with AMI and 52 healthy controls (HCs) were involved in this study. The levels of NETs, fragment a of the factor B (Ba), fragment a of the 5th complement (C5a) and myeloperoxidase (MPO) in peripheral blood were detected by enzyme linked immunosorbent assay (ELISA) at the onset of AMI [pre-treatment (PRT) group], post-operative treatment group (POT group) and in HC group. Their differences between the groups were detected by t test while the relationships between the parameters in PRT group were tested by Pearson correlation analysis. Results All the parameters from PRT and POT group were higher than those in the HC group, respectively. The levels of cardiac troponin I (cTnI), NETs, Ba, C5a and MPO in PRT group were higher than those in POT group [(0.279±0.132) ng/ml vs.(0.016±0.008) ng/ml, P < 0.001; OD value: (0.466±0.143) vs. (0.378±0.151), P=0.002; (72.812±30.144) pg/ml vs. (60.491±28.323) pg/ml, P=0.001; (327.112±203.228) ng/ml vs. (260.411±135.984) ng/ml, P=0.025; (75.782±33.596) ng/ml vs. (58.462±29.647) ng/ml, P=0.008, respectively]. In PRT group, NETs was positively correlated with Ba, C5a and MPO (r=0.394, P=0.001; r=0.324, P=0.030 and r=0.406, P < 0.001), respectively, and Ba had positive correlation with C5a (r=0.436, P < 0.001) while cTnI was only correlated with NETs (r=0.352, P=0.008). The cTnI level, though recovered to normal range in POT group, was still higher than that in HC group [(0.016±0.008) pg/ml vs. (0.012±0.007) pg/ml, P=0.016]. Conclusions The persistent high level of NETs and its related high activity of complement alternative pathway in CAHD during the onset of AMI and post-treatment of CABG might contribute to the progression of the disease and the recurrence of myocardial infarction. Intervention on the formation of NETs might be one of the potential pathways to prevent the progression of CHAD and the occurrence of AMI.
- Coronary atherosclerotic heart disease /
- Acute myocardial infarction /
- Coronary artery bypass graft /
- Neutrophil extracellular traps /
- Pathogenesis

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表 1 研究对象cTnI、NETs、Ba、C5a及MPO水平的组间比较(x±s)

Table 1. Comparison of cTnI, nets, Ba, C5a and MPO levels among subjects (x±s)

项目	AMI组(N=52)		HC组(N=52)	P值^a	P值^b	P值^c
项目	PRT组	POT组	HC组(N=52)	P值^a	P值^b	P值^c
cTnI (ng/ml)	0.279±0.132	0.016±0.008	0.012±0.007	< 0.001	< 0.001	0.016
NETs (OD值)	0.466±0.143	0.378±0.151	0.273±0.150	0.002	< 0.001	0.006
Ba (pg/ml)	72.812±30.144	60.491±28.323	50.072±18.258	0.001	< 0.001	0.028
C5a (ng/ml)	327.112±203.228	260.411±135.984	203.232±68.813	0.025	< 0.001	0.008
MPO (ng/ml)	75.782±33.596	58.462±29.647	42.206±24.802	0.008	< 0.001	0.003
注：^a PRT组与POT组间配对t检验的P值；^b PRT组与HC组间t检验的P值；^c POT组与HC组间t检验的P值。

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表 2 PRT组相关指标相关性

Table 2. Correlation of related indexes in PRT group

项目	cTnI	年龄	NETs	Ba	C5a	MPO
cTnI	1.000	0.054	0.352 ^a	0.137	0.112	0.033
年龄	-	1.000	0.091	0.104	0.239	0.056
NETs	-	-	1.000	0.394 ^a	0.324 ^a	0.406 ^a
Ba	-	-	-	1.000	0.436 ^a	0.125
C5a	-	-	-	-	1.000	0.040
MPO	-	-	-	-	-	1.000
注：^a P < 0.05。

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