陈筱涵;郁琦;
CHEN Xiao-han;YU Qi;Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College;

• 1:中国医学科学院北京协和医学院北京协和医院妇产科

摘要(Abstract)：

雌激素是一种多功能甾体类激素,不仅对女性生殖系统,且对内分泌、心血管、代谢系统等均具有明显作用。雌激素对多种肺部疾病具有潜在治疗价值,雌激素受体信号转导在呼吸道病毒感染过程中,参与机体固有免疫、适应性免疫、组织修复过程。动物实验证实,雌激素可以降低炎性因子水平,抑制炎症反应,降低病毒滴度等,从而提高呼吸道病毒感染小鼠的存活率。本文探讨雌激素对于呼吸道病毒感染的保护作用及其机制。
Estrogen is a multi-functional steroid hormone, which affects not only the female reproductive system, but also endocrine, cardiovascular, and metabolic systems. Estrogen has a potential therapeutic effect on a variety of lung diseases, and estrogen-receptor signaling plays a key role in the innate immunity, adaptive immunity and tissue repair in the course of infection of respiratory virus. Animal experiments have proved that estrogen therapy can reduce inflammatory factors, inhibit inflammatory response, reduce viral titer and so on, so as to improve the survival rate of mice infected with respiratory virus. In this paper, the protective effect of estrogen on the infection of respiratory virus and related mechanisms were reviewed.

关键词(KeyWords)： 呼吸道感染;病毒;雌激素;保护机制
respiratory infection;virus;estrogen;protective mechanism

Abstract:

Keywords:

基金项目(Foundation): 国家重点研发计划(2018YFC1002105)~~

作者(Authors): 陈筱涵;郁琦;
CHEN Xiao-han;YU Qi;Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College;

参考文献(References)：

• [1] Lai CC,Shih TP,Ko WC,et al.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) and coronavirus disease- 2019 (COVID- 19):The epidemic and the challenges[J].Int J Antimicrob Agents,2020,55:105924.
• [2] Sathish V,Martin YN,Prakash YS.Sex steroid signaling:implications for lung diseases[J].Pharmacol Ther,2015,150:94- 108.
• [3] Jin JM,Bai P,He W,et al.Gender Differences in Patients With COVID- 19:Focus on Severity and Mortality[J].Front Public Health,2020,8:152.
• [4] Alghamdi IG,Hussain,II,Almalki SS,et al.The pattern of Middle East respiratory syndrome coronavirus in Saudi Arabia:a descriptive epidemiological analysis of data from the Saudi Ministry of Health[J].Int J Gen Med,2014,7:417- 423.
• [5] Leung GM,Hedley AJ,Ho LM,et al.The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic:an analysis of all 1755 patients[J].Ann Intern Med,2004,141:662- 673.
• [6] Hamming I,Timens W,Bulthuis ML,et al.Tissue distribution of ACE2 protein,the functional receptor for SARS coronavirus.A first step in understanding SARS pathogenesis[J].J Pathol,2004,203:631- 637.
• [7] Xu X,Chen P,Wang J,et al.Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission[J].Sci China Life Sci,2020,63:457- 460.
• [8] Zhang X,Li S,Niu S.ACE2 and COVID- 19 and the resulting ARDS[J].Postgrad Med J,2020,96:403- 407.
• [9] Zhao Y,Zhao ZX,Wang YJ,et al.Single-Cell RNA Expres-sion Profiling of ACE2,the Receptor of SARS-CoV- 2[J].Am J Respir Crit Care Med,2020,202:756- 759.
• [10] Ding Y,Wang H,Shen H,et al.The clinical pathology of severe acute respiratory syndrome (SARS):a report from China[J].J Pathol,2003,200:282- 289.
• [11] 李红芳，郭彦青，王元，等.一半是天使，一半是魔鬼：ACE2在新型冠状病毒肺炎易感性和急性肺损伤肺保护中的辩证关系[J].临床心血管病杂志，2020,36:400- 405.[11] Li HF,Guo YQ,Wang Y,et al.Angel goes beside satan:the bipuasic role of ACE2 on the susceptibility and virulence of severe acute respiratory syndrome coronavirus- 2 and the potentially protective efficiency against acute lung injury[J].Lin Chuang Xin Xue Guan Bing Za Zhi,2020,36:400- 405.
• [12] Pons S,Fodil S,Azoulay E,et al.The vascular endothelium:the cornerstone of organ dysfunction in severe SARS-CoV- 2 infection[J].Crit Care,2020,24:353.
• [13] Shi X,Guan Y,Jiang S,et al.Renin-angiotensin system inhibitor attenuates oxidative stress induced human coronary artery endothelial cell dysfunction via the PI3K/AKT/mTOR pathway[J].Arch Med Sci,2019,15:152- 164.
• [14] Bansal R,Gubbi S,Muniyappa R.Metabolic Syndrome and COVID 19:Endocrine-Immune-Vascular Interactions Shapes Clinical Course[J].Endocrinology,2020,161:bqaa112.
• [15] Franks TJ,Chong PY,Chui P,et al.Lung pathology of severe acute respiratory syndrome (SARS):a study of 8 autopsy cases from Singapore[J].Hum Pathol,2003,34:743- 748.
• [16] Wong CK,Lam CW,Wu AK,et al.Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome[J].Clin Exp Immunol,2004,136:95- 103.
• [17] Channappanavar R,Fehr AR,Vijay R,et al.Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice[J].Cell Host Microbe,2016,19:181- 193.
• [18] Guan WJ,Liang WH,Zhao Y,et al.Comorbidity and its impact on 1590 patients with COVID- 19 in China:a nationwide analysis[J].Eur Respir J,2020,55:2000547.
• [19] Kovats S.Estrogen receptors regulate innate immune cells and signaling pathways[J].Cell Immunol,2015,294:63- 69.
• [20] Smith EP,Boyd J,Frank GR,et al.Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man[J].N Engl J Med,1994,331:1056- 1061.
• [21] 秦川，鲍琳琳，邓巍，等.血管紧张素转换酶2在SARS-CoV感染中的功能(第2部分)--SARS-CoV在ACE2表达细胞中的复制和ACE2基因敲除对小鼠SARS-CoV感染的保护作用[J].中国比较医学杂志，2005,15:330- 334.[21] Qin C,Bao LL,Deng W,et al.The Role of Converting Enzyme 2 in SARS-CoV Infection (Part Ⅱ)--The Replication of SARS-CoV in Murine Fibroblasts Expressing Human ACE2 and the Protective Effect of ACE2 Knockout on SARS Infection in Mice[J].Zhongguo Bi Jiao Yi Xue Za Zhi,2005,15:330- 334.
• [22] Rey-Parra GJ,Vadivel A,Coltan L,et al.Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury[J].J Mol Med (Berl),2012,90:637- 647.
• [23] Lin CI,Tsai CH,Sun YL,et al.Instillation of particulate matter 2.5 induced acute lung injury and attenuated the injury recovery in ACE2 knockout mice[J].Int J Biol Sci,2018,14:253- 265.
• [24] Imai Y,Kuba K,Rao S,et al.Angiotensin-converting enzyme 2 protects from severe acute lung failure[J].Nature,2005,436:112- 116.
• [25] Brosnihan KB,Hodgin JB,Smithies O,et al.Tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor-alpha knock-out mice[J].Exp Physiol,2008,93:658- 664.
• [26] Stelzig KE,Canepa-Escaro F,Schiliro M,et al.Estrogen regulates the expression of SARS-CoV- 2 receptor ACE2 in differentiated airway epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2020,318:L1280-L1281.
• [27] Feng Q,Li L,Wang X.Identifying Pathways and Networks Associated With the SARS-CoV- 2 Cell Receptor ACE2 Based on Gene Expression Profiles in Normal and SARS-CoV- 2-Infected Human Tissues[J].Front Mol Biosci,2020,7:568954.
• [28] Vermillion MS,Ursin RL,Attreed SE,et al.Estriol Reduces Pulmonary Immune Cell Recruitment and Inflammation to Protect Female Mice From Severe Influenza[J].Endocrinology,2018,159:3306- 3320.
• [29] Channappanavar R,Fett C,Mack M,et al.Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection[J].J Immunol,2017,198:4046- 4053.
• [30] Robinson DP,Lorenzo ME,Jian W,et al.Elevated 17beta-estradiol protects females from influenza A virus pathogenesis by suppressing inflammatory responses[J].PLoS Pathog,2011,7:e1002149.
• [31] Nguyen DC,Masseoud F,Lu X,et al.17beta-Estradiol restores antibody responses to an influenza vaccine in a postmenopausal mouse model[J].Vaccine,2011,29:2515- 2518.
• [32] Pazos MA,Kraus TA,Munoz-Fontela C,et al.Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice[J].PLoS One,2012,7:e40502.
• [33] Robinson DP,Hall OJ,Nilles TL,et al.17beta-estradiol protects females against influenza by recruiting neutrophils and increasing virus-specific CD8 T cell responses in the lungs[J].J Virol,2014,88:4711- 4720.
• [34] Raberg L,Sim D,Read AF.Disentangling genetic variation for resistance and tolerance to infectious diseases in animals[J].Science,2007,318:812- 814.
• [35] Sims AC,Baric RS,Yount B,et al.Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia:role of ciliated cells in viral spread in the conducting airways of the lungs[J].J Virol,2005,79:15511- 15524.
• [36] Peretz J,Pekosz A,Lane AP,et al.Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female,but not male,donors[J].Am J Physiol Lung Cell Mol Physiol,2016,310:L415-L425.
• [37] Hui KPY,Cheung MC,Perera R,et al.Tropism,replica-tion competence,and innate immune responses of the coronavirus SARS-CoV- 2 in human respiratory tract and conjunctiva:an analysis in ex-vivo and in-vitro cultures[J].Lancet Respir Med,2020,8:687- 695.
• [38] Scarpitta AM,Sinagra D.Polycystic ovary syndrome:an endocrine and metabolic disease[J].Gynecol Endocrinol,2000,14:392- 395.
• [39] Mauvais-Jarvis F,Manson JE,Stevenson JC,et al.Menopausal Hormone Therapy and Type 2 Diabetes Prevention:Evidence,Mechanisms,and Clinical Implications[J].Endocr Rev,2017,38:173- 188.
• [40] Heine PA,Taylor JA,Iwamoto GA,et al.Increased adipose tissue in male and female estrogen receptor-alpha knockout mice[J].Proc Natl Acad Sci U S A,2000,97:12729- 12734.
• [41] Srivaratharajah K,Abramson BL.Hypertension in meno-pausal women:the effect and role of estrogen[J].Menopause,2019,26:428- 430.