首页|基于hACE2转导建立SARS-CoV-2 spike假病毒感染病证结合的小鼠病毒肺炎模型

基于hACE2转导建立SARS-CoV-2 spike假病毒感染病证结合的小鼠病毒肺炎模型

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目的 建立与评价一种安全、经济、有效的病证结合小鼠新冠病毒感染肺炎模型.方法 30只KM种小鼠随机分为空白组、对照组及实验1组、实验2组、实验3组,每组各6只.每天把KM小鼠置于模拟寒湿环境中4 h,将表达hACE2的重组腺相关病毒(pAAV-hACE2)采用改良悬挂法气管内给药转导至肺组织,继以新型冠状病毒(SARS-CoV-2)spike假病毒采用相同的气管内给药方式造模.观察各组小鼠一般情况,检测体重变化、肺指数、血清炎性因子及肺部病理变化.结果 免疫组化法显示hACE2在小鼠肺组织中有效表达;在寒湿环境中给予SARS-CoV-2 spike假病毒后,实验组小鼠表现出类似疫毒犯肺证候的体征;且同样喂养条件和时间下,与空白组和对照组小鼠比较,实验组小鼠出现体重下降;实验1、2、3组小鼠出现肺指数显著增大(P<0.05或P<0.01),血清炎性因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)显著升高(P<0.01),肺组织病理改变明显.结论 本研究成功建立了一种安全、经济、有效的病证结合小鼠新冠病毒感染肺炎模型.
Establishment of SARS-CoV-2 Spike Pseudovirus Infected Mice Pneumonia Model Based on hACE2 Transduction
Objective:To establishment and evaluate a safe,economical and effective disease syndrome model of mouse COVID-19 infected pneumonia.Methods:30 KM mice were randomly divided into the blank group,control group,experimental 1,2,3 groups,with 6 mice in each group.KM mice were placed in a simulated cold and humid environment for 4 hours every day,and the recombinant adeno-associated virus expressing hACE2 was transferred into the lung tissue of KM mice by the improved intratracheal administration method,and then the mod-el was made by the same intratracheal administration method of SARS-CoV-2 spike pseudovirus.The general situ-ation of mice in each group was observed,and the changes of body weight,lung index,serum inflammatory factors and lung pathology were detected.Results:Immunohistochemistry showed that hACE2 was effectively expressed in mouse lung tissue;the mice in the experimental group showed signs similar to the lung syndrome caused by epi-demic virus after being given SARS-CoV-2 spike pseudovirus in cold and wet environment;under the same feed-ing conditions and time,compared with the blank group and the control group,the experimental group showed weight loss;the lung index of mice in groups 1,2 and 3 increased significantly(P<0.05 or P<0.01),the levels of serum inflammatory factor IL-1β,IL-6,IL-8,TNF-α were significantly increased(P<0.01),and the pathological changes of lung tissue were obvious.Conclusion:This study has successfully established a safe,economical and effective model of mouse COVID-19 infection pneumonia combined with disease and syndrome.

COVID-19(SARS-CoV-2)spike pseudovirusRecombinant adeno-associated virus(pAAV-hACE2)Cold and damp epidemic pestilenceCombination of disease and syndromeViralPneumoniaMouse ani-mal model

邱敏、陈欢、江飞龙、朱青、刘莉

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重庆中医药学院第一附属医院,重庆市中医院,重庆 400021

重庆中医药学院,重庆 400032

重庆医科大学,重庆 401331

新型冠状病毒(SARS-CoV-2)spike假病毒 重组腺相关病毒(pAAV-hACE2) 寒湿疫 病证结合 病毒 肺炎 小鼠动物模型

2024

中国中医急症
中华中医药学会

中国中医急症

CSTPCD
影响因子:1.144
ISSN:1004-745X
年,卷(期):2024.33(9)