目的 探究壮宣饮通过调节 p38 丝裂原活化蛋白激酶（p38 mitogen-activated protein kinase，p38 MAPK）信 号介导的肠道菌群治疗小儿甲型流感病毒 H1N1 肺炎的机制。方法 取 BALB/c 小鼠采用 H1N1 流感病毒尿囊 液滴鼻法制备 H1N1 肺炎小鼠模型，随机分为 5 组：模型组，壮宣饮低、中、高剂量组，壮宣饮高剂量 （28.66 g·kg-1）+茴香霉素（10 mg·kg-1）组。对照组采用同法滴入等体积无菌生理盐水。使用壮宣饮和茴香霉素分 组处理后，测定各组小鼠肺系数并以 HE 染色检测其肺与大肠组织病理形态；以 16SrRNA 基因测序检测各组 小鼠肠道菌群结构差异改变；以酶联免疫吸附法（ELASA）测定各组小鼠肺泡灌洗液（BALF）及大肠组织中炎症 因子肿瘤坏死因子 α（TNF-α）、白细胞介素（IL）-4、IL-6、IL-1β 水平；以蛋白免疫印迹法检测各组小鼠肺与 大肠组织中 p38 MAPK 通路相关蛋白表达。结果 与对照组比较，模型组小鼠肺与大肠组织发生明显病理损 伤，肺系数，肺与大肠病理评分，ACE 指数，Shannon 指数，梭菌目丰度，肺泡灌洗液与大肠组织中 TNF-α、 IL-4、IL-6、IL-1β 水平，肺与大肠组织 p-p38 MAPK/p38 MAPK 水平均升高（P＜0.05）；拟杆菌目丰度降低 （P＜0.05）。与模型组比较，壮宣饮低、中、高剂量组小鼠肺与大肠组织病理损伤均减轻，肺系数，肺与大肠 病理评分，ACE 指数，Shannon 指数，梭菌目丰度，肺泡灌洗液与大肠组织 TNF-α、IL-4、IL-6、IL-1β 水 平，肺与大肠组织 p-p38 MAPK/p38 MAPK 水平均降低（P＜0.05），且均呈剂量依赖性（P＜0.05）。拟杆菌目丰 度均升高（P＜0.05），与壮宣饮高剂量组比较，壮宣饮高剂量+茴香霉素组小鼠肺与大肠组织病理损伤加重，肺 系数，肺与大肠病理评分，ACE 指数，Shannon 指数，梭菌目丰度，肺泡灌洗液与大肠组织 TNF-α、IL-4、 IL-6、IL-1β 水平，肺与大肠组织 p-p38 MAPK/p38 MAPK 水平均升高（P＜0.05）；拟杆菌目丰度降低（P＜ 0.05）。结论 壮宣饮可通过抑制 p38 MAPK 信号激活而改善 H1N1 肺炎小鼠肠道菌群失衡，从而抑制小鼠炎 症并减轻其肺与大肠组织损伤，对小儿 H1N1 肺炎起到治疗作用。

Objective To explore the mechanism of Zhuangxuan Yin in the treatment of children with H1N1 pneumonia through regulating gut microbiota mediated by p38 mitogen-activated protein kinase （p38-MAPK） pathway. Methods A BALB/c mouse model of H1N1 pneumonia was prepared using the H1N1 influenza virus allantoic solution for nasal drop. The model was randomly separated into 5 groups：model group，Zhuangxuan Yin low-，medium- and high- dose groups，and high-dose Zhuangxuan Yin（28.66 g·kg-1）+ anisomycin（10 mg·kg-1） group. The control group was infused with sterile physiological saline of equal volume using the same method. After treatment with Zhuangxuan Yin and anisomycin， the lung index of mice in each group was measured， and HE staining was applied to detect the pathological morphology of lung and large intestine tissues. 16SrRNA gene sequencing was applied to detect the structural difference of gut microbiota in mice of each group. Enzyme-linked immunosorbent assay （ELASA） was applied to measure the levels of tumor necrosis factor- α （TNF- α）， interleukin （IL）-4，IL-6，and IL-1β in bronchoalveolar lavage fluid （BALF） and large intestine tissue of mice in each group. Western Blot was applied to detect the expression of p38-MAPK pathway-related proteins in lung and large intestine tissues of mice in each group. Results Compared with the control group，the lung and large intestine tissues of the model group mice showed obvious pathological damage，the lung index，pathological score of lung and large intestine，ACE index，Shannon index，abundance of class Clostridia，the levels of TNF- α，IL-4，IL-6， and IL-1β in BALF and large intestine tissues，and p-p38-MAPK/p38-MAPK in lung and large intestine tissues increased （P＜0.05）. The abundance of class Bacteroidales decreased （P＜0.05） . Compared with the model group， the pathological damage in the lung and large intestine tissues of mice in the Zhuangxuan Yin low-，medium- and high- dose groups were reduced. The lung index， pathological score of lung and large intestine， ACE index， Shannon index，abundance of class Clostridia，the levels of TNF-α，IL-4，IL-6，and IL-1β in BALF and large intestine tissues， and p-p38-MAPK/p38-MAPK in lung and large intestine tissues decreased （P＜0.05）， the abundance of class Bacteroidales increased （P＜0.05），and in a dose-dependent manner （P＜0.05） . Compared with the high-dose Zhuangxuan Yin group，the pathological damage in the lung and large intestine tissues of mice in the high-dose Zhuangxuan Yin+anisomycin group was aggravated，the lung index，pathological score of lung and large intestine，ACE index，Shannon index，abundance of class Clostridia，the levels of TNF- α，IL-4，IL-6， and IL-1β in BALF and large intestine tissues，and p-p38-MAPK/p38-MAPK in lung and large intestine tissues increased （P＜0.05），and the abundance of class Bacteroidales decreased （P＜0.05） . Conclusion Zhuangxuan Yin can improve the imbalance of intestinal microbiota in H1N1 pneumonia mice by inhibiting p38-MAPK signal activation，thereby inhibiting inflammation and reducing lung and large intestine tissue damage in mice，which may have a therapeutic effect on children with H1N1 pneumonia.

R285.5

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