基于免疫调节探讨葛根汤颗粒治疗小鼠病毒性肺炎的作用机制

doi:10.19803/j.1672-8629.20230612

中国药物警戒 ›› 2024, Vol. 21 ›› Issue (2): 132-136.
DOI: 10.19803/j.1672-8629.20230612

• 基于多模型、多靶点的中药抗感染药效及机制研究专栏（一） • 上一篇下一篇

基于免疫调节探讨葛根汤颗粒治疗小鼠病毒性肺炎的作用机制

赵荣华¹, 孙静¹, 包蕾¹, 耿子涵¹, 陶夏莉², 张敬升¹, 庞博¹, 徐英莉¹, 曹姗¹, 李舒冉¹, 郭姗姗¹, 王道涵^3#, 崔晓兰^1,*

¹中国中医科学院中药研究所生物安全实验室,北京 100700;
²北京瑞诺众德科技有限公司,北京 100095;
³北京中医药大学东方医院儿科,北京 100078

收稿日期:2023-09-26 出版日期:2024-02-15 发布日期:2024-02-06
通讯作者: ^*崔晓兰,女,博士,研究员,中药防治感染性疾病机制研究。E-mail：cuixiaolan2812@126.com。^#为共同通信作者。
作者简介:赵荣华,女,博士,副研究员·硕导,中药防治病毒性疾病药效机制研究。
基金资助:
中国中医科学院创新工程重点项目（CI2021A04606）; 国家重点研发计划（2020YFE0205100）

Mechanisms of Gegen Tang granules against viral pneumonia in mice based on immune regulation

ZHAO Ronghua¹, SUN Jing¹, BAO Lei¹, GENG Zihan¹, TAO Xiali², ZHANG Jingsheng¹, PANG Bo¹, XU Yingli¹, CAO Shan¹, LI Shuran¹, GUO Shanshan¹, WANG Daohan^3#, CUI Xiaolan^1,*

¹Biosecurity Laboratory, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
²Beijing Reno Technology Co., Ltd., Beijing 100095 China;
³Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China

Received:2023-09-26 Online:2024-02-15 Published:2024-02-06

摘要/Abstract

摘要： 目的研究葛根汤颗粒对甲型流感病毒（influenza A virus,IAV）致小鼠病毒性肺炎模型的药效评价及免疫调节作用。方法 ICR小鼠,13~15 g,分为正常对照组、模型对照组,磷酸奥司他韦阳性药对照组及葛根汤颗粒高、中、低剂量组(6.6、3.3、1.7 g^-1·kg^-1·d^-1）,每组10只,采用IAV（FM1株）病毒液感染建立小鼠病毒性肺炎模型,同时给予相关药物治疗。观察各组小鼠肺指数及肺指数抑制率,RT-PCR法检测肺组织核酸,ELISA法检测小鼠肺组织因子白介素-6（IL-6）、白介素-10（IL-10）、肿瘤坏死因子TNF-α;同时采用IAV（FM1株）病毒液滴鼻感染小鼠,造成死亡保护模型,观察小鼠感染后2周内的死亡情况,计算小鼠的死亡率、死亡保护率、平均存活天数和生命延长率。结果葛根汤颗粒中剂量组肺指数及肺组织病毒载量显著降低（P<0.01）,肺指数抑制率为50.73%;葛根汤颗粒高、中剂量组肺组织炎性因子IL-10含量显著降低（P<0.01）、葛根汤颗粒中、低剂量组肺组织炎性因子TNF-α含量显著降低（P<0.01）;葛根汤颗粒3个剂量组肺组织炎性因子IL-6含量显著降低（P<0.01）;模型组小鼠死亡率90%,平均存活天数9.45 d,葛根汤颗粒3个剂量组小鼠死亡率显著降低、平均存活天数显著延长,生命延长率显著提高（P<0.01）。结论葛根汤颗粒可通过调节模型小鼠免疫炎性因子水平达到改善病毒性肺炎小鼠免疫功能的作用,同时可显著降低模型小鼠肺指数和肺组织病毒载量,从而减轻模型小鼠的肺部炎性损伤;对模型小鼠有死亡保护作用。

关键词: 甲型流感病毒, 葛根汤颗粒, 炎性因子, 免疫调节, 死亡保护, 肺指数, 小鼠

Abstract: Objective To study the efficacy and immunomodulatory effects of Gegen Tang granules on viral pneumonia induced by influenza A virus (IAV) in mice. Methods ICR mice, 13~15 g, were divided into the normal control group, model control group, oseltamivir phosphate positive control group and high-, medium- and low-dose Gegen Tang granule groups (6.6, 3.3 and 1.7 g^-1·kg^-1·d^-1), with 10 mice in each group. A viral pneumonia model of mice was established by IAV (FM1 strain) while relevant medication was given. Lung indexes and their inhibitory rate were observed. Levels of nucleic acid in lung tissue were detected by RT-PCR, while interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor TNF-α in lung tissue were detected by ELISA. AV (FM1 strain) virus was used to infect mice with nasal drops, resulting in a death protection model. The death toll of mice within 2 weeks of infection was observed, and the mortality rate, death protection rate, average survival days and life extension rate of mice were calculated. Results The pulmonary index and viral load of lung tissue were significantly decreased (P<0.01), and the inhibitory rate of lung indexes was 50.73%. The content of lung inflammatory factor IL-10 in high and medium dose groups of Gegen Tang granules was significantly decreased (P<0.01), so was the content of lung inflammatory factor TNF-α in medium and low dose groups of Gegen Tang granules (P<0.01). The content of inflammatory factor IL-6 in lung tissue was significantly decreased in the three dose groups of Gegen Tang granules (P<0.01). The mortality rate of mice in the model group was 90%, and the average survival was 9.45 days, both of which were significantly decreased in the three dose groups of Gegen Tang granules, while the life extension rate was significantly increased (P<0.01). Conclusion Gegen Tang granules can improve the immune function of mice with viral pneumonia by adjusting the level of immune inflammatory factors while significantly reducing the lung index and viral load of the model mice so as to alleviate the pulmonary inflammatory damage to the model mice. They can help protect model mice from death.

Key words: influenza A virus, Gegen Tang granules, inflammatory factors, immune regulation, death protection, lung index, mice

中图分类号:

赵荣华, 孙静, 包蕾, 耿子涵, 陶夏莉, 张敬升, 庞博, 徐英莉, 曹姗, 李舒冉, 郭姗姗, 王道涵, 崔晓兰. 基于免疫调节探讨葛根汤颗粒治疗小鼠病毒性肺炎的作用机制[J]. 中国药物警戒, 2024, 21(2): 132-136.

ZHAO Ronghua, SUN Jing, BAO Lei, GENG Zihan, TAO Xiali, ZHANG Jingsheng, PANG Bo, XU Yingli, CAO Shan, LI Shuran, GUO Shanshan, WANG Daohan, CUI Xiaolan. Mechanisms of Gegen Tang granules against viral pneumonia in mice based on immune regulation[J]. Chinese Journal of Pharmacovigilance, 2024, 21(2): 132-136.

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基于免疫调节探讨葛根汤颗粒治疗小鼠病毒性肺炎的作用机制

Mechanisms of Gegen Tang granules against viral pneumonia in mice based on immune regulation

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