中国药物警戒 ›› 2025, Vol. 22 ›› Issue (9): 986-993.
DOI: 10.19803/j.1672-8629.20250183

• 基础与临床研究 • 上一篇    下一篇

清解防感颗粒对人冠状病毒229E湿热疫毒袭肺小鼠的预防作用

韩曼1, 许晶2, 赵荣华3, 耿子涵3, 年霞4, 冯晓兰1, 刘帅1, 宋延平1,*   

  1. 1陕西省中医药研究院,陕西 西安 710003;
    2渭南市检验检测研究院,陕西 渭南 714000;
    3中国中医科学院中药研究所,北京 100700;
    4陕西中医药大学,陕西 咸阳 712046
  • 收稿日期:2025-03-27 发布日期:2025-09-22
  • 通讯作者: *宋延平,男,学士,研究员,中药药理研究。E-mail: sypdd2003@163.com
  • 作者简介:韩曼,女,硕士,主管中药师,中药药理研究。
  • 基金资助:
    国家自然科学基金资助项目（82305078）; 陕西省中医药管理局中医药防治新冠病毒科研攻关项目（ZYJXG-Y23009）

Preventive Effect of Qingjie Fanggan Granules on Mice with Human Coronavirus 229E-Induced Dampness-Heat Epidemic Toxin Attacking Lung

HAN Man1, XU Jing2, ZHAO Ronghua3, GENG Zihan3, NIAN Xia4, FENG Xiaolan1, LIU Shuai1, SONG Yanping1,*   

  1. 1Shaanxi Institute of Traditonal Chinese Medicine, Xi’an Shaanxi 710003, China;
    2Weinan Inspection and Testing Institute,Weinan Shaanxi 714000, China;
    3Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
    4Shaanxi University of Chinese Medicine, Xianyang Shaanxi 712046, China
  • Received:2025-03-27 Published:2025-09-22

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摘要： 目的 通过建立人冠状病毒229E湿热疫毒袭肺小鼠模型,模拟新型冠状病毒感染的中医症候,观察预防给予清解防感颗粒对该病症结合小鼠模型的作用,探索其对新型冠状病毒感染的可能作用。方法 60只BALB/C小鼠,随机分为正常组、湿毒组、湿热组、病毒组、清解防感颗粒高/低剂量组（8.2/4.1 g·kg-1·d-1）,采用湿热环境和229E滴鼻感染小鼠造模,建立人冠状病毒229E湿热疫毒袭肺病症结合小鼠模型,给药组从小鼠放入湿热环境时开始给药,直至229E病毒感染前,229E病毒感染后第2天解剖小鼠,摘取肺脏、脾脏。计算肺脏、脾脏指数及肺抑制率,RT-PCR法检测肺组织病毒载量,并检测肺脏、脾脏病理情况,ELISA检测肺组织中炎症因子IL-6、TNF-α、IL-1β及IL-8的含量水平。WB法检测肺组织中MAPK信号通路中P-p38、p38蛋白的表达量。结果 与湿毒组比较,清解防感颗粒显著降低人冠状病毒229E湿热疫毒袭肺小鼠肺指数（P<0.01）;升高脾指数（P<0.05）,高、低剂量组肺指数抑制率分别为61.73%和71.15%;能够显著降低肺组织病毒载量（P<0.01）、减轻肺组织病变（P<0.01或P<0.05）,改善脾组织病理改变;显著降低小鼠肺组织中IL-6、TNF-α、IL-1β及IL-8的含量水平（P<0.01或P<0.05）及MAPK通路中P-p38蛋白表达（P<0.05）。结论 预防给予清解防感颗粒,能够减轻人冠状病毒229E湿热疫毒袭肺模型小鼠肺部炎症,其作用机制可能与抑制p38蛋白磷酸化及MAPK通路有关。

关键词: 清解防感颗粒, 冠状病毒, 预防作用, 病症结合, 炎症因子, p38蛋白, MAPK通路, 小鼠

Abstract: Objective To observe the effect of preventive administration of Qingjie Fanggan Granules on this disease-model combination, and explore its possible role in COVID-19 by establishing a mouse model of human coronavirus 229E infection with dampness-heat pestilential toxin attacking the lung, which simulates the TCM syndromes of COVID-19 infection. Methods Sixty BALB/C mice were randomly divided into normal control group, dampness-toxin control group, dampness-heat control group, virus control group, and high/low dose groups of Qingjie Fanggan Granules (8.2/4.1 g·kg-1·d-1). The syndrome-combined model of human coronavirus 229E was established by modeling mice with a damp-heat environment and intranasal infection of 229E. The administration groups were given the drug starting from when the mice were placed in the damp-heat environment until before 229E virus infection. Mice were sacrificed 1 day after 229E virus infection, and lungs and spleens were harvested. Calculate lung and spleen indices, lung inhibition rate. Detect viral load in lung tissues by RT-PCR, observe pathological changes of lung and spleen. Detect levels of inflammatory factors IL-6, TNF-α, IL-1β and IL-8 in lung tissues by ELISA. Detect expressions of P-p38 and p38 proteins in p38 MAPK signaling pathway of lung tissues by Western Blot. Results Compared with the dampness-toxin control group, Qingjie Fanggan Granules significantly reduced the lung index (P<0.01) and increased the spleen index (P<0.05) in mice with damp-heat pestilential toxin attacking the lung infected by human coronavirus 229E. The lung index inhibition rates of high and low-dose groups were 61.73% and 71.15% respectively. It could significantly reduce the viral load in lung tissues (P<0.01), alleviate lung tissue lesions (P<0.01 or P<0.05), improve splenic tissue pathological changes, and significantly decrease the levels of IL-6, TNF-α, IL-1β and IL-8 in lung tissues (P<0.01 or P<0.05), as well as the expression of P-p38 protein in the MAPK pathway (P<0.05). Conclusion Preventive administration of Qingjie Fanggan Granules can alleviate lung inflammation caused by HCoV-229E infection, and its mechanism may be related to the inhibition of p38 protein phosphorylation and the MAPK signaling pathway.

Key words: Qingjie Fanggan Granules, Coronavirus, Preventive Effect, Combination of Disease and Syndrome, Inflammatory Factor, p38, MAPK Signaling Pathway, Mice

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