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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2022, Vol. 15 ›› Issue (02) : 157 -160. doi: 10.3877/cma.j.issn.1674-6902.2022.02.004

论著

膜联蛋白A2在病毒性社区获得性肺炎中的表达及意义
陈瑶1, 陈复辉2,†()   
  1. 1. 150001　哈尔滨，哈尔滨医科大学附属第二医院呼吸内科；448000　荆门，荆门市第一人民医院呼吸与危重症医学科
    2. 150001　哈尔滨，哈尔滨医科大学附属第二医院呼吸内科
  • 收稿日期:2021-05-25 出版日期:2022-04-25
  • 通信作者: 陈复辉
  • 基金资助:
    国家科技重大专项(2017ZX10103004-009)

Expression and significance of annexin A2 in patients with viral community-acquired pneumonia

Yao Chen1, Fuhui Chen2,†()   

  1. 1. Department of Respiratory Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China; Department of Respiratory and Critical Care Medicine, Jingmen First People′s Hospital, Jingmen 448000, China
    2. Department of Respiratory Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China
  • Received:2021-05-25 Published:2022-04-25
  • Corresponding author: Fuhui Chen
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引用本文：

陈瑶, 陈复辉. 膜联蛋白A2在病毒性社区获得性肺炎中的表达及意义[J]. 中华肺部疾病杂志(电子版), 2022, 15(02): 157-160.

Yao Chen, Fuhui Chen. Expression and significance of annexin A2 in patients with viral community-acquired pneumonia[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(02): 157-160.

目的

分析病毒性社区获得性肺炎(CAP)患者外周血单个核细胞(PMBCs)中膜联蛋白A2的表达差异，为病毒性肺炎治疗提供新思路。

方法

选取2016年1月至2018年1月我院住院治疗的病毒性CAP患者50例为病毒组，细菌性CAP患者47例为细菌组，同时选取健康体检者48例为对照组。采用实时荧光定量聚合酶链反应(qPCR)法测定患者PBMCs中膜联蛋白A2 mRNA的表达水平，采用蛋白免疫印迹(Western-blot)方法检测患者PBMCs中膜联蛋白A2蛋白的表达水平，分析病毒组中ANXA2表达的差异性。

结果

病毒组中单一病毒感染40例，混合病毒感染10例。单一病毒感染中流感病毒(30%)感染比例最高，其次为鼻病毒和冠状病毒，7例混合病毒感染包含了流感病毒。病毒组和细菌组的膜联蛋白A2 mRNA表达高于对照组，且病毒组膜联A2 mRNA的表达高于细菌组，有统计学意义(P<0.05)，冠状病毒组ANXA2的mRNA和蛋白的表达较细菌性CAP组和对照组均增加，有统计学意义(P<0.05)。

结论

ANXA2可能通过更多的途径及机制参与病毒性肺炎的发生，ANXA2在冠状病毒感染中的作用可能更显著，ANXA2可成为病毒性CAP尤其是冠状病毒性CAP抗病毒治疗靶点。

关键词: 病毒性肺炎, 冠状病毒, 膜联蛋白A2
Objective

To investigate the expression of Annexin A2 in peripheral blood mononuclear cells of patients with viral community-acquired pneumonia, and provide new ideas for the antiviral treatment of viral pneumonia.

Methods

A total of 50 patients with viral CAP and 47 patients with bacterial CAP who were hospitalized in our hospital from January 2016 to January 2018 were selected as the virus group and bacteria group, respectively, and 48 healthy patients were selected as the control group. The quantitative real-time polymerase chain reaction (qPCR) method was used to determine the expression level of annexin A2 mRNA, and the western-blot method was used to detect the expression level of annexin A2 protein. Compare the relative expression levels of each group.

Results

There were 40 cases of single virus infection and 10 cases of mixed virus infection in the virus group. Influenza virus (30%) accounted for the highest proportion of single virus infections, followed by rhinoviruses and coronaviruses, and 7 mixed virus infections included influenza viruses. The expression of annexin A2 mRNA in the viral group and the bacterial group was higher than that in the control group, and the expression of the viral group was higher than that of the bacterial group. The difference was statistically significant (P<0.05). The expression of mRNA and protein of ANXA2 in the coronavirus group was higher than that of the bacterial CAP group and the control group. The difference was statistically significant (P<0.05).

Conclusion

ANXA2 may participate in the occurrence of viral CAP through more ways and mechanisms. The role of ANXA2 in coronavirus infection may be more significant. ANXA2 has the potential to become a target of antiviral therapy for viral CAP, especially coronavirus CAP.

Key words: Viral pneumonia, Coronavirus, Annexin A2
表1 引物序列
基因名 上游引物序列(5′-3′) 下游引物序列(5′-3′)
ANXA2 TCTCTATGACGCTGGAGTGAAG AACCTCTTTCCTGATGCTTTC
β-actin GGCACCCAGCACAATGAA GGAAGGTGGACAGCGAGG
表2 50例病毒性CAP的呼吸道病原体检测结果
病原体结果 例数 病原体结果 例数
甲型流感病毒 12 人副流感病毒 1
鼻病毒 9 冠状病毒+甲型流感病毒 3
冠状病毒 8 鼻病毒+人副流感病毒 2
乙型流感病毒 3 鼻病毒+腺病毒 1
腺病毒 2 乙型流感病毒+甲型流感病毒 1
人偏肺病毒 2 甲型流感病毒+肠道病毒 1
呼吸道合胞病毒 2 甲型流感病毒+鼻病毒 1
肠道病毒 1 鼻病毒+甲型流感病毒+冠状病毒 1
图1 膜联蛋白A2 mRNA在对照组、细菌组和病毒组中的相对表达量。注：对照组vs.病毒组vs.细菌组，**P<0.01；对照组vs.细菌组，*P<0.05；对照组vs.病毒组，**P<0.01，病毒组vs.细菌组，*P<0.05
图2 膜联蛋白A2在对照组、细菌组和冠状病毒组中的表达。注：A：ANXA2 mRNA的相对表达量通过qPCR法测定，用β-actin作为内参基因，将对照组相对表达量进行均"1"化处理，结果显示冠状病毒性CAP的PBMCs中ANXA2表达增加(对照组vs.细菌组vs.冠状病毒组，P<0.01)；B：用Western-blot法测定ANXA2蛋白表达量，同样以β-actin作为内参蛋白，结果也显示冠状病毒性CAP的PBMC中ANXA2表达增加
1
Lanks CW, Musani AI, Hsia DW. Community-acquired pneumonia and hospital-acquired pneumonia[J]. Med Clin North Am, 2019, 103(3): 487-501.
2
Burk M, El-Kersh K, Saad M, et al. Viral infection in community-acquired pneumonia: a systematic review and meta-analysis[J]. Eur Respir Rev, 2016, 25(140): 178-188.
3
Rider AC, Frazee BW. Community-acquired pneumonia[J]. Emerg Med Clin North Am, 2018, 36(4): 665-683.
4
Cavallazzi R, Ramirez JA. Influenza and viral pneumonia[J]. Clin Chest Med, 2018, 39(4): 703-721.
5
Jain S. Epidemiology of viral pneumonia[J]. Clin Chest Med, 2017, 38(1): 1-9.
6
Dandachi D, Rodriguez-Barradas MC. Viral pneumonia: etiologies and treatment[J]. J Investig Med, 2018, 66(6): 957-965.
7
窦　唱，李兴旺. 社区获得性病毒性肺炎病原学治疗研究进展[J]. 中国病毒病杂志，2018, 8(5): 421-426.
8
Bharadwaj A, Bydoun M, Holloway R, et al. Annexin A2 heterotetramer：structure and function[J]. Int J Mol Sci, 2013, 14(3): 6259-6305.
9
Dallacasagrande V, Hajjar KA. Annexin A2 in inflammation and host defense[J]. Cells, 2020, 9(6): 1499.
10
Schloer S, Pajonczyk D, Rescher U. Annexins in translational research：hidden treasures to be found[J]. Int J Mol Sci, 2018, 19(6): 1781.
11
Taylor JR, Skeate JG, Kast WM. Annexin A2 in virus infection[J]. Front Microbiol, 2018, 9: 2954.
12
LeBouder F, Morello E, Rimmelzwaan GF, et al. Annexin Ⅱ incorporated into influenza virus particles supports virus replication by converting plasminogen into plasmin [J]. J Virol, 2008, 82(14): 6820-6828.
13
LeBouder F, Lina B, Rimmelzwaan GF, et al. Plasminogen promotes influenza A virus replication through an annexin 2-dependent pathway in the absence of neuraminidase[J]. J Gen Virol, 2010, 91(Pt 11): 2753-2761.
14
Su H, Yang X, Wang S, et al. Effect of annexin Ⅱ-mediated conversion of plasmin from plasminogen on airborne transmission of H9N2 avian influenza virus[J]. Vet Microbiol, 2018, 223: 100-106.
15
Ma Y, Sun J, Gu L, et al. Annexin A2 (ANXA2) interacts with nonstructural protein 1 and promotes the replication of highly pathogenic H5N1 avian influenza virus[J]. BMC Microbiol, 2017, 17(1): 191.
16
Fang YT, Lin CF, Liao PC, et al. Annexin A2 on lung epithelial cell surface is recognized by severe acute respiratory syndrome-associated coronavirus spike domain 2 antibodies[J]. Mol Immunol, 2010, 47(5): 1000-1009.
17
Malhotra R, Ward M, Bright H, et al. Isolation and characterisation of potential respiratory syncytial virus receptor(s) on epithelial cells[J]. Microbes Infect, 2003, 5(2): 123-133.
18
Derry MC, Sutherland MR, Restall CM, et al. Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5[J]. J Gen Virol, 2007, 88(Pt 1): 19-27.
19
Koga R, Kubota M, Hashiguchi T, et al. Annexin A2 Mediates the localization of measles virus matrix protein at the plasma membrane[J]. J Virol, 2018, 92(10): e00181-18.
20
Heyraud S, Jaquinod M, Durmort C, et al. Contribution of annexin 2 to the architecture of mature endothelial adherens junctions[J]. Mol Cell Biol, 2008, 28(5): 1657-1668.
21
Luo M, Flood EC, Almeida D, et al. Annexin A2 supports pulmonary microvascular integrity by linking vascular endothelial cadherin and protein tyrosine phosphatases[J]. J Exp Med, 2017, 214(9): 2535-2545.
22
Swisher JF, Khatri U, Feldman GM. Annexin A2 is a soluble mediator of macrophage activation[J]. J Leukoc Bio, 2007, 82(5): 1174-1184.
23
Song C, Zhou X, Dong Q, et al. Regulation of inflammatory response in human chondrocytes by lentiviral mediated RNA interference against S100A10[J]. Inflamm Res, 2012, 61(11): 1219-1227.
24
Laumonnier Y, Syrovets T, Burysek L, et al. Identification of the annexin A2 heterotetramer as a receptor for the plasmin-induced signaling in human peripheral monocytes[J]. Blood, 2006, 107(8): 3342-3349.
25
Li Q, Ke F, Zhang W, et al. A role for the annexin A2 amino-terminal peptide in the plasmin-induced activation of human peripheral monocytes[J]. Mol Immunol, 2010, 47(14): 2405-2410.
26
Li Q, Laumonnier Y, Syrovets T, et al. Plasmin triggers cytokine induction in human monocyte-derived macrophages[J]. Arterioscler Thromb Vasc Biol, 2007, 27(6): 1383-1389.
27
Swisher JF, Burton N, Bacot SM, et al. Annexin A2 tetramer activates human and murine macrophages through TLR4[J]. Blood, 2010, 115(3): 549-558.
28
Zhang S, Yu M, Guo Q, et al. Annexin A2 binds to endosomes and negatively regulates TLR4-triggered inflammatory responses via the TRAM-TRIF pathway[J]. Sci Rep, 2015, 5: 15859.
29
瞿介明，曹　彬. 中国成人社区获得性肺炎诊断和治疗指南(2016年版)[J]. 中华结核和呼吸杂志，2016, 39(4): 253-279.
30
何丽艳. 54例社区获得性肺炎病原学分析[D]. 中国医科大学，2018: 23-45.
31
刘馨玉，李　萌，陈明伟，等. 成人社区获得性肺炎住院患者的病原学分析[J]. 临床医学研究与实践，2019, 4(29): 20-21.
32
陈　静，李晓光，王　伟，等. 成人社区获得性肺炎病原学特点分析[J]. 中华急诊医学杂志，2020, 29(9): 1210-1213.
33
刘　熙，李　琦. 我国成人社区获得性肺炎诊疗现状及思考[J/CD]. 中华肺部疾病杂志(电子版), 2021, 14(3): 387-389.
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