金振口服液对人冠状病毒肺炎热毒疫幼龄小鼠模型的干预机制  

Effect of Jinzhen oral liquid on the model of human coronavirus pneumonia and fever epidemic immature adult mice

作　　者：赵荣华[1] 孙静[1] 包蕾[1] 耿子涵 李贵平[2,3] 王道涵 李舒冉[1] 张敬升 庞博 徐英莉[1] 周利润 鲍岩岩 陈梦苹[1] 郭姗姗 崔晓兰[1] ZHAO Ronghua;SUN Jing;BAO Lei;GENG Zihan;Li Guiping;WANG Daohan;LI Shuran;ZHANG Jingsheng;PANG Bo;XU Yingli;ZHOU Lirun;BAO Yanyan;CHEN Mengping;GUO Shanshan;CUI Xiaolan(Biosecurity Laboratory,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Jiangsu Kanion Pharmaceutical CO.,LTD.,Lianyungang Jiangsu 222001,China;State Key Laboratory of New Technology for Pharmaceutical Process of Traditional Chinese Medicine,Lianyungang Jiangsu 222001,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,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 [2]江苏康缘药业股份有限公司,江苏连云港222001 [3]中药制药过程新技术国家重点实验室,江苏连云港222001 [4]北京中医药大学东方医院儿科,北京100078

出　　处：《中国药物警戒》2023年第3期248-252,257,共6页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(2021YFC1712903);中国中医科学院创新工程重大攻关项目资金资助(CI2021A04606)。

摘　　要：目的研究金振口服液对人冠状病毒肺炎热毒疫幼龄小鼠模型的干预作用。方法ICR小鼠,分为空白组,人冠状病毒229E(HCoV-229E)感染组,中医热证组,人冠状病毒肺炎热毒疫小鼠模型组,磷酸氯喹组,连花清瘟组及金振口服液高、中、低剂量组(30、15和7.5 mL·kg^(-1)·d^(-1),相当于生药8、4和2 g·kg^(-1)·d^(-1)),每组10只,采用热湿环境复合HCoV-229E感染造模及给药。观察小鼠的肺指数和抑制率,肺组织核酸,ELISA法检测小鼠肺组织因子IL-1β、MDA及下丘脑因子PGE2、CAMP,流式细胞术检测小鼠外周血免疫细胞比例。结果金振口服液中剂量组可显著降低模型小鼠肺指数(P<0.01),肺指数抑制率为43.93%;金振口服液高、中剂量组可显著降低模型小鼠肺组织病毒载量、IL-1β含量(P<0.05,P<0.01)、中剂量组可显著降低模型小鼠MDA水平(P<0.01);金振口服液3个剂量组可显著降低模型小鼠下丘脑中PGE2、CAMP的生成(P<0.05,P<0.01);对外周血免疫细胞百分比无显著影响。结论金振口服液可明显改善人冠状病毒肺炎热毒疫幼龄小鼠的免疫功能,表现为通过抑制肺组织中炎性细胞因子表达而缓解肺部炎性损伤,可显著降低模型小鼠肺指数和病毒载量,同时可下调体温调节中枢因子的表达,对模型小鼠的肺部炎症起到干预作用。Objective To study the therapeutic effect of Jinzhen oral liquid against a human coronavirus pneumonia and fever epidemic immature adult mouse model.Methods ICR mice were divided into the blank group,HCoV-229E infection group,TCM heat syndrome group,human coronavirus pneumonia and fever epidemic mouse model group,chloroquine phosphate group,Lianhua Qingwen group and Jinzhen oral liquid high-dose,medium-dose and low-dose groups(30 mL·kg^(-1)·d^(-1),15 mL·kg^(-1)·d^(-1),7.5 mL·kg^(-1)·d^(-1)),with 10 mice in each.HCoV-229E infection was used for modeling and administration.Lung indexes and inhibition rates of mice were observed.The nucleic acid of lungs was detected by ELISA.IL-1β,while MDA and hypothalamus factors PGE2 and CAMP by flow cytometry.Results The lung index of model mice in the Jinzhen oral liquid medium dose group was significantly reduced(P<0.01),and the inhibition rate of the lung index was 43.93%.The viral load and IL-1βin lung tissues of model mice were significantly reduced in the Jinzhen oral liquid highdose and medium-dose groups(P<0.05,P<0.01).MDA in lung tissues of model mice was significantly reduced in the medium-dose group(P<0.01).The production of PGE2 and CAMP in the hypothalamus of model mice was significantly inhibited in the Jinzhen oral liquid group(P<0.05,P<0.01).The percentage of peripheral blood immune cells was not significantly affected.Conclusion Jinzhen oral liquid can significantly improve the immunity of the coronavirus pneumonia and fever epidemic mouse model by inhibiting the inflammatory cytokine expression in lung tissues,mitigating lung inflammatory injury,reducing significantly the lung index and viral load,and lowering the expression of temperature-regulating central factors.

关 键 词：金振口服液 人冠状病毒肺炎 热毒疫 幼龄小鼠 炎性因子 免疫调节 肺指数 肺指数抑制率 

分 类 号：R978.7[医药卫生—药品] R965.1[医药卫生—药学] R969.3