中国药物警戒 ›› 2025, Vol. 22 ›› Issue (5): 488-494.
DOI: 10.19803/j.1672-8629.20250031

• 中药抗感染作用机制研究专栏 • 上一篇    下一篇

散寒化湿颗粒对流感病毒与呼吸道合胞病毒致小鼠肺炎模型的作用机理研究

赵荣华1, 朱春旭, 孙静1, 包蕾1, 王馨蔚1, 耿子涵1, 张敬升1, 郭姗姗1, 李舒冉1, 王道涵2#, 崔晓兰1,*   

  1. 1中国中医科学院中药研究所,北京 100700;
    2北京中医药大学东方医院儿科,北京 100078
  • 收稿日期:2025-01-14 出版日期:2025-05-15 发布日期:2025-05-19
  • 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,副研究员·硕导,中药药效作用机制研究。Δ为并列第一作者。
  • 基金资助:
    国家自然科学基金资助项目(82305078); 中国中医科学院科技创新工程(C12021A04606)

Mechanisms of Sanhan Huashi Granules on a Respiratory Syncytial Virus and Influenza Virus and Respiratory Syncytial Virus Induced Pneumonia Model in Mice

ZHAO Ronghua1, ZHU Chunxu, SUN Jing1, BAO Lei1, WANG Xinwei1, GENG Zihan1, ZHANG Jingsheng1, GUO Shanshan1, LI Shuran1, WANG Daohan2#, CUI Xiaolan1,*   

  1. 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;
    2Department of Pediatrics, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China
  • Received:2025-01-14 Online:2025-05-15 Published:2025-05-19

摘要: 目的 研究散寒化湿颗粒对小鼠感染甲型H1N1流感病毒及呼吸道合胞病毒(RSV)所致肺炎模型的治疗作用机理。方法 通过采用甲型H1N1流感病毒FM1(H1N1/FM1)毒株及RSV以滴鼻的方式感染小鼠,构建病毒性肺炎小鼠模型;建模后,取小鼠肺组织,计算小鼠的肺指数及其抑制率。甲型H1N1流感病毒感染模型及RSV感染模型均设立正常组,模型组,连花清瘟组,散寒化湿高剂量组(52.8 g·kg-1·d-1)、中剂量组(26.4 g·kg-1·d-1)、低剂量组(13.2 g·kg-1·d-1),甲型H1N1流感病毒感染模型以奥司他韦组为模型组,RSV感染模型利巴韦林组为模型组,建模并给药后,针对甲型H1N1流感病毒FM1毒株感染的小鼠,将其肺内细支气管及肺组织进行苏木精-伊红(HE)染色处理,在显微镜下详细观察病变情况,并依据既定的标准进行等级评分,并对RSV滴鼻感染小鼠的肺组织中白细胞介素-4(IL-4)、白细胞介素-33(IL-33)的水平进行检测。结果 散寒化湿颗粒中剂量组可显著降低H1N1/FM1模型组小鼠肺指数(P<0.05),显著改善小鼠肺内细支气管及肺组织的病变程度,肺部及支气管病变等级显著降低。散寒化湿颗粒高剂量组可显著降低RSV感染小鼠肺指数(P<0.05),且散寒化湿颗粒3个剂量组均可明显升高RSV感染小鼠IL-4含量、降低IL-33含量,模型组、散寒化湿低剂量组、中剂量组及高剂量组的IL-4含量依次为(50.20±2.22)、)、(61.63±1.34)、(71.46±2.39)、(56.74±1.24)pg·mL-1,IL-33含量依次为(1 787.37±60.59)、(1 273.10±378.04)、(1 532.38±337.96)、(1 347.33±345.39)pg·mL-1,均与模型组比较,差异具有统计学意义(P<0.01,P<0.05)。结论 散寒化湿颗粒可改善小鼠肺内细支气管及肺组织的病变程度,使肺部及支气管病变等级显著降低,显著降低病毒性肺炎模型小鼠的肺指数,且能使得小鼠肺脏IL-4含量升高、IL-33含量降低。

关键词: 散寒化湿颗粒, 甲型H1N1流感病毒, 呼吸道合胞病毒, 病毒性肺炎, 小鼠

Abstract: Objective To study the therapeutic mechanism of Sanhan Huashi granules (SHG) on a pneumonia model induced by influenza A (H1N1) virus and respiratory syncytial virus (RSV) in mice. Methods The mice were infected with the FM1 strain of influenza A (H1N1) virus and respiratory syncytial virus (RSV) by nasal drip to construct a mouse model of viral pneumonia. Both influenza A (H1N1) virus group and the RSV group were divided into normal group, model group, Lianhua Qingwen group(LHG), SHG groups with high-dose(52.8 g·kg-1·d-1), medium-dose(26.4 g·kg-1·d-1), and low-dose (13.2 g·kg-1·d-1). And oseltamivir group was served as the control group in the influenza A (H1N1) virus group, ribavirin group was served as the control group in the RSV group. After modelling and intragastric administration, the lung tissues of the mice were taken to accurately calculate the lung index and its inhibition rate. For mice infected with the FM1 strain of influenza A (H1N1) virus, hematoxylin-eosin (HE) staining was performed on the bronchioles and lung tissues. The pathological changes were observed under a microscope, and the grades were scored by the established standards. At the same time, the levels of interleukin-4 (IL-4) and interleukin-33 ( IL-33 ) in lung tissues of mice infected with RSV were detected. Results A medium dose of SHG could significantly reduce the lung index of mice in the H1N1/FM1 model group (P <0.05), improve the pathological changes of bronchioles and lung tissues, and reduce the grade of lung and bronchial lesions while a high dose of SHG could significantly reduce the lung index of RSV-infected mice (P<0.05). The three doses of SHG could significantly increase the content of IL-4 but reduce the content of IL-33 in RSV-infected mice. The contents of IL-4 in the model group, the low-dose group, the medium-dose group and the high-dose group were(50.20±2.22),(61.63±1.34),(71.46±2.39)and(56.74±1.24)pg·mL-1 respectively, compared with(1 787.37±60.59), (1 273.10±378.04), (1 532.38±337.96) and(1 347.33±345.39)pg·mL-1 for IL-33, all of which were significantly different from those of the control group (P<0.01, P<0.05). Conclusion SHG can mitigate the severity of pathological changes of bronchioles and lung tissues of mice, significantly reduce the grade of lung and bronchial lesions, significantly lower the lung index of viral pneumonia in model mice, and increase the content of IL-4 in the lungs of mice while decreasing the content of IL-33.

Key words: Sanhan Huashi Granules, H1N1 Influenza A Virus, Respiratory Syncytial Virus, Viral Pneumonia, Mice

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