基于TLR7-MyD88-IRAK4信号通路的解表清里方体内抗甲型流感病毒的实验研究  

Experimental Study on the in Vivo Anti-Influenza A Virus of Jiebiao Qingli Formula Based on the TLR7-MyD88-IRAK4 Signaling Pathway

作　　者：马一川 明雨 姚睿祺 晁燕 张洪春[5] MA Yichuan;MING Yu;YAO Ruiqi;CHAO Yan;ZHANG Hongchun(Beijing University of Chinese Medicine,Beijing 100029,China;Institute of Clinical Basic Medicine of Traditional Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Shenzhen Nanshan District Hospital of Traditional Chinese Medicine,Shenzhen 518000,China;Beijing Oriental Yungjia Pharmaceutical Co,Ltd,Beijing 100029,China;Clinical Research Center for Respiratory Diseases,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京100029 [2]中国中医科学院中医临床基础医学研究所,北京100700 [3]深圳市南山区中医院,广东深圳518000 [4]北京东方运嘉药业有限公司,北京100029 [5]中日友好医院呼吸疾病临床研究中心,北京100029

出　　处：《中医药学报》2024年第6期18-23,共6页Acta Chinese Medicine and Pharmacology

基　　金：国家重点研发计划项目(2022YFC3500800);中国中医科学院流感防治技术体系(ZZ13-025-06)。

摘　　要：目的:探讨中药复方解表清里方体内抑制甲型H1N1流感病毒株复制的作用及机制。方法:使用随机数字法,将132只SPF级小鼠平均分为空白组、模型组、磷酸奥司他韦组(剂量为0.0375 g/kg)、解表清里方高、中、低剂量组(剂量分别为6.05、3.02和1.51 g/kg),每组22只。空白组不进行任何操作,用甲型流感病毒[A/Brisbane/02/2018(H1N1),pdm09-like virus(H1N1)]滴鼻法感染其他组小鼠,在造模2 h后,空白组和模型组用生理盐水灌胃,其他组给予相应剂量的药物,各组灌胃7 d。给药期间每日定期检测小鼠体质量及活动状态,在造模第3天和第7天取材,检测小鼠肺指数和肺部病理改变;qPCR法检测肺组织中病毒核酸载量;蛋白质印迹法检测造模第7天小鼠肺组织中TLR7、MyD88和IRAK4蛋白表达水平。结果:解表清里方可以减轻全身症状,降低肺指数,延缓小鼠体质量下降(P<0.05,P<0.01),改善肺组织病理损伤,降低鼠肺病毒滴度(P<0.01),上调肺组织中TLR7、MyD88和IRAK4蛋白表达量(P<0.05,P<0.01),其中解表清里方高剂量组的疗效最优。结论:解表清里方可剂量依赖性改善小鼠肺部感染、降低病毒复制,其机制可能与TLR7-MyD88-IRAK4信号通路有关。Objective:To investigate the effect and mechanism of Jiebiao Qingli formula(JQF)on in vivo inhibiting the reproduction of H1N1 influenza virus strain.Methods:Using the random number method,112 SPF-grade mice were equally divided into a blank group,a model group,an oseltamivir phosphate group(0.0375 g/kg),and JQF high-,medium-,and low-dose groups(6.05,3.02,and 1.51 g/kg,respectively),with 22 mice in each group.The blank group was not subjected to any intervention,and the remaining groups of mice were infected with influenza A virus[A/Brisbane/02/2018(H1N1),pdm09-like virus(H1N1)]by nasal drip method.Two hours after modeling,the blank group and model group were given normal saline by gavage,the other groups were given correspanding doses of medication,and each group was given intragastric administration for 7 days.The body weights and activity status of the mice were examined daily at regular intervals during the administration period.Samples were taken from the mice on day 3 and day 7 of the modeling,and the lung index and pathological changes of the lungs were detected.The viral nucleic acid load in the lung tissues was detected by qT-PCR,and Western blotting was used to detect the protein expression levels of TLR7,MyD88,and IRAK4 in the lung tissues of the mice on day 7 of the modeling period.Results:JQF could alleviate the systemic symptoms,reduce the lung index,delay the weight loss of the mice(P<0.05),improve the pathological damage of lung tissues,reduce the viral titer in the murine lungs(P<0.05),and up-regulate the protein expression of TLR7,MyD88 and IRAK4 in lung tissues,with the best efficacy in the high-dose group of JQF.Conclusion:Jiebiao Qingli formula can dose-dependently improve lung infection and reduce viral replication in mice,and its mechanism may be related to the TLR7-MyD88-IRAK4 signaling pathway.

关 键 词：解表清里方 TOLL样受体7 A型流感病毒 动物实验 抗病毒 

分 类 号：R285.5[医药卫生—中药学]