人冠状病毒229E湿热疫毒袭肺病证结合小鼠模型的建立及评价  

Establishment and evaluation of a mouse model combining disease with syndrome of HCoV-229E pneumonia with lung-attacking damp-heat syndrome

作　　者：庞博[1] 张敬升 郭姗姗[1] 孙静[1] 包蕾[1] 徐英莉 曹姗 陈梦苹 王雅欣 赵荣华[1] 崔晓兰[1] PANG Bo;ZHANG Jingsheng;GUO Shanshan;SUN Jing;BAO Lei;XU Yingli;CAO Shan;CHEN Mengping;WANG Yaxin;ZHAO Ronghua;CUI Xiaolan(Biosecurity Laboratory,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中药研究所生物安全实验室,北京100700

出　　处：《中国药物警戒》2023年第1期40-45,共6页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(2021YFC1712903)。

摘　　要：目的在采用外部湿热因素造成中医湿毒袭肺小鼠模型的基础上,同时采用人冠状病毒229E(HCoV-229E)感染小鼠造成肺炎模型,建立湿热疫毒袭肺病症结合小鼠模型。方法对湿热感染不同天数的小鼠中医证候表征、肺指数和肺部病毒载量、肺部病理结构与影像学、小鼠血清胃泌素(Gas)、下丘脑前列腺素E2(PGE2)、环磷酸腺苷(c AMP)及肌糖原评价湿毒疫动物模型。结果人冠状病毒肺炎湿热疫毒袭肺证小鼠病证结合模型小鼠饮食量下降和饮水量增加,毛发枯燥发黄,行动迟缓爱扎堆,大便便溏。肺指数增加(P<0.01),肺部病毒核酸呈阳性表达,肺组织可见病理结构变化及斑点状阴影。小鼠体内肌糖原含量、血清胃泌素含量、下丘脑c AMP、PGE2的含量在感染后均有显著升高(P<0.05)。结论本研究建立的HCoV-229E湿热疫毒袭肺证病证结合小鼠模型与临床疾病表征具有一致性,可为诊断及治疗具有该证候的病毒性肺炎与开发相关药物研究提供一种可靠的评价动物模型。Objective To establish a disease-syndrome pneumonia mouse model of lung-attacking damp-heat virus caused by external damp-heat stimulation and human coronavirus HCoV-229E virus infection.Methods The animal model of damp-heat epidemic was evaluated in terms of TCM syndrome,lung indexes and viral loads,pathological structure and imaging of the lung,the contents of serum gastrin(Gas),prostaglandin E2(PGE2),cyclic adenosine monophosphate(cAMP)in the hypothalamus and muscle glycogen of mice infected with damp-heat virus for different days.Results This mouse model showed that the mice’s diet decreased while water consumption increased,and that their fur became dull and yellow,movements sluggish,and stool loose.The lung index increased(P<0.01),the viral nucleic acid in the lung was positively expressed,and pathological changes and speckled shadows were observed in the lung tissue.The contents of muscle glycogen,serum gastrin,hypothalamic cAMP and prostaglandin E2 in mice increased significantly after infection(P<0.05).Conclusion The mouse model of HCoV-229E and damp-heat stimulation established in this study is consistent with clinical symptoms,which can serve as a reliable animal evaluation model for emergency screening or research of drugs for treating viral pneumonia with this syndrome.

关 键 词：人冠状病毒229E 湿热疫毒袭肺 病毒性肺炎 中医证候 动物模型 

分 类 号：R996[医药卫生—毒理学] R994.11[医药卫生—药学]