荆银双解散基于PI3K/AKT信号通路治疗甲型流感病毒感染小鼠的作用机制研究  

Mechanism of Jingyin Shuangjie Powder in the treatment of influenza A virus-infected mice based on PI3K/AKT signaling pathway

作　　者：郭雨菲 王成祥 孙慧媛 王明哲[4] 翟志光[5] 李磊 薛贝 程锦涛 马媛虹 黄廷轩 于会勇 GUO Yufei;WANG Chengxiang;SUN Huiyuan;WANG Mingzhe;ZHAI Zhiguang;LI Lei;XUE Bei;CHENG Jintao;MA Yuanhong;HUANG Tingxuan;YU Huiyong(Beijing University of Chinese Medicine,Beijing 100029,China;Respiratory Department of Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029;Internet Hospital Office of Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029;Respiratory Department of Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700;Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700;Infectious Diseases Department of Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学第三附属医院呼吸科,北京100029 [3]北京中医药大学第三附属医院互联网诊疗办公室,北京100029 [4]北京中医药大学东直门医院呼吸科,北京100700 [5]中国中医科学院中医基础理论研究所,北京100700 [6]北京中医药大学第三附属医院感染科,北京100029

出　　处：《北京中医药》2025年第1期68-75,共8页Beijing Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82074389);北京中医药大学第三附属医院培育项目(BZYSY-2022-PYMS-19)。

摘　　要：目的基于脂酰肌醇3激酶(PI3K)/丝氨酸苏氨酸激酶(AKT)信号通路探讨荆银双解散治疗甲型流感病毒感染小鼠的作用机制。方法将96只小鼠按照随机数字表法分为空白组、模型组、西药组和中药组,各24只,进行药效学研究;另选25只小鼠按照随机数字表法分为空白组、模型组、中药组、通路激动剂组、通路激动剂联合中药组,各5只,进行机制研究。除空白组外,其他各组建立流感病毒亚洲甲型鼠肺适应株PR8感染小鼠模型,中药组予荆银双解散3 mg/(g·d)灌胃,西药组予磷酸奥司他韦22.75 mg/(kg·d)灌胃,通路激动剂组予胰岛素样生长因子-1(IGF-1)50μg/(kg·d)腹腔注射,通路激动剂联合中药组予IGF-150μg/(kg·d)腹腔注射+荆银双解散3 mg/(g·d)灌胃,1次/d。药效学研究中,比较连续给药1、3、5 d时,各组小鼠一般情况、肺指数与肺指数抑制率、肺组织病理变化,ELISA法检测各组肺组织IL-6、IL-10、IFN-γ水平;机制研究中,连续给药5 d,Western blotting法检测各组肺组织PI3K、p-AKT、AKT、NF-κB p65蛋白相对表达量,RT-qPCR法检测各组PI3K、AKT、NF-κB p65 mRNA表达量。结果与模型组比较,中药组小鼠一般状态较好,体质量、饮食量较多,给药第3、5天肺指数低(P<0.05),肺组织炎性浸润和红细胞渗出轻。与模型组比较,中药组第3天肺组织IL-6相对表达量低(P<0.05)、IL-10相对表达量高(P<0.05),给药第3、第5天肺组织IFN-γ相对表达量低(P<0.05)。与模型组比较,中药组PI3K、p-AKT/AKT、NF-κB p65蛋白相对表达量低(P<0.05),PI3K、AKT、NF-κB mRNA相对表达量低(P<0.05);与中药组比较,通路激动剂联合中药组PI3K、p-AKT/AKT、NF-κB p65蛋白和PI3K、AKT、NF-κB p65 mRNA相对表达量高(P<0.05)。结论荆银双解散能够改善甲型流感病毒感染小鼠一般情况,降低小鼠肺指数,改善细胞因子表达及小鼠肺部病理损伤,其作用机制可能为下调PI3K/AKT信号通路关键蛋白和基Objective To explore the mechanism of Jingyin Shuangjie Powder(JYSJ)in treating influenza A virus infection in mice based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods A total of 96 mice were randomly divided into the blank group,model group,western medicine group,and Chinese medicine group according to a random number table,with 24 mice in each group for pharmacodynamics study.Another 25 mice were randomly divided into the blank group,model group,Chinese medicine group,pathway agonist group,and pathway agonist combined with Chinese medicine group according to a random number table,with 5 mice in each group for the mechanism study.Except for the blank group,all other groups were established with a model of influenza virus(Asian type mouse lung-adapted strain PR8)infection.Mice in the Chinese medicine group were administered JYSJ[3 mg/(g·d)]via intragastric administration,mice in the western medicine group were given oseltamivir phosphate[22.75 mg/(kg·d)]via intragastric administration,mice in the pathway agonist group were given insulin-like growth factor-1(IGF-1)[50μg/(kg·d)]via intraperitoneal injection,and mice in the pathway agonist combined with Chinese medicine group were administered IGF-1[50μg/(kg·d)]via intraperitoneal injection plus JYSJ[3 mg/(g·d)]via intragastric administration,once per day.In the pharmacodynamics study,after 1,3,and 5 days of continuous administration,the general condition,lung index,lung index inhibition rate,and pathological changes in lung tissue were compared.The levels of IL-6,IL-10,and IFN-γin lung tissue were detected by ELISA.In the mechanism study,after 5 days of continuous administration,the relative expression levels of PI3K,p-AKT,AKT,and NF-κB p65 proteins in lung tissue were detected by Western blot,and the mRNA expression levels of PI3K,AKT,and NF-κB p65 were detected by RT-qPCR.Results Compared with the model group,the general condition of the mice in the Chinese medicine group was better,with higher body weight and foo

关 键 词：甲型流感病毒 荆银双解散 细胞因子风暴 脂酰肌醇3激酶/丝氨酸苏氨酸激酶信号通路 小鼠 

分 类 号：R73[医药卫生—肿瘤]