清开灵注射液治疗冠状病毒肺炎的作用机制研究  

The Mechanism of Qingkailing Injection against Coronavirus Pneumonia

作　　者：郭姗姗[1] 赵荣华[1] 耿子涵 包蕾[1] 孙静[1] 时宇静[1] 鲍岩岩[1] 高英杰[1] 崔晓兰[1] GUO Shanshan;ZHAO Ronghua;GENG Zihan;BAO Lei;SUN Jing;SHI Yujing;BAO Yanyan;GAO Yingjie;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》2021年第12期1111-1116,共6页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(81773977);国家自然科学基金培育专项(ZXKT20025)。

摘　　要：目的基于湿热疫毒袭肺病证结合小鼠模型,研究清开灵注射液治疗冠状病毒肺炎的作用机制。方法实验设正常组,人冠状病毒229E(HCoV-229E)感染组,湿热组,病证结合模型组,阳性药组(0.09g/(kg·d))和清开灵注射液高(1.47 mL/(kg·d))、中(0.77 mL/(kg·d))、低(0.37 mL/(kg·d))剂量组,计算各组肺指数、肺指数抑制率,采用RT-PCR检测小鼠肺组织中病毒载量,Elisa法检测下丘脑和肺组织中发热介质、炎症因子和氧化应激因子水平,流式细胞术检测外周血免疫细胞百分比。结果与模型组相比,清开灵注射液中、低剂量组的肺指数(P<0.05,P<0.01)和肺部病毒载量明显降低(P<0.01,P<0.05);3个剂量组肺部CD14、IL-1β和下丘脑PGE2、cAMP含量降低(P<0.01),中、低剂量组肺部MDA含量也降低(P<0.01,P<0.05),高、中剂量组肺部SOD含量升高(P<0.01);3个剂量组外周血中CD4_(+)T细胞、CD8^(+)T细胞和B细胞占比均显著降低(P<0.01,P<0.05)。结论清开灵注射液可通过调节免疫功能、抑制细胞因子风暴、减少自由基堆积等对冠状病毒肺炎湿热疫毒袭肺病证结合小鼠模型发挥治疗作用。Objective To investigate the mechanism of Qingkailing Injection in the treatment of coronavirus pneumonia based on mouse model combining disease and syndrome of human coronavirus pneumonia with heat-dampness pestilence attacking the lung.Methods BALB/c mice were randomly divided into eight groups,including normal group,HCoV-229 E infection group,Heat-dampness group,model group,positive drug group(0.09 g/(kg·d)),Qingkailing Injection high-dose group(1.47 mL/(kg·d)),middle-dose group(0.73 mL/(kg·d))and low-dose group(0.37 m L/(kg·d)).The viral load in lung tissue was detected by RT-PCR,the febrile mediators,inflammatory factors and oxidative stress factors in hypothalamus and lung tissue were detected by ELISA,the percentage of immune cells in peripheral blood was detected by flow cytometry.Results Compared with the model,middle-dose and low-dose groups of Qingkailing Injection can reduce the lung index(P<0.05,P<0.01)and the viral load in lung tissue(P<0.01,P<0.05).Three dose groups of Qingkailing Injection reduce the contents of CD14 and IL-1βin lung tissue(P<0.01),the middle-and low-dose groups reduce the content of MDA(P<0.01,P<0.05),the high-dose and middle-dose groups increase the content of SOD(P<0.01),and the three dose groups of Qingkailing Injection could reduce the proportion of CD4^(+)T cells,CD8^(+)T cells and B cells in peripheral blood(P<0.01,P<0.05).Conclusion Qingkailing Injection can play a therapeutic role in this model by regulating immune function,inhibiting cytokine storm and reducing the accumulation of free radicals.

关 键 词：清开灵注射液 湿热疫毒袭肺 人冠状病毒229E 细胞因子 免疫调节 

分 类 号：R994.11[医药卫生—毒理学]