(–)-萜品-4-醇抗人呼吸道合胞病毒感染的动物试验研究  

Animal Study of(–)-Terpinen-4-ol against Human Respiratory Syncytial Virus Infection

作　　者：郭名扬 陶玲 沈祥春 王建新[3] 罗语思 张科 GUO Mingyang;TAO Ling;SHEN Xiangchun;WANG Jianxin;LUO Yusi;ZHANG Ke(Key and Characteristic Lab.of Modern Pathogenicity Biology,Dept.of Human Parasitology,School of Basic Medicine,Guizhou Medical University,Guiyang 550025;The Hight Efficacy Application of Natural Medicine Resources Engineering Center of Guizhou Province,School of Pharmaceutical Sciences,Guizhou Medical University,Guiyang 550025;School of Pharmacy,Fudan University,Shanghai 201203;Dept.of Emergency,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004)

机构地区：[1]贵州医科大学基础医学院,人体寄生虫学教研室,现代病原生物学特色重点实验室,贵州贵阳550025 [2]贵州医科大学药学院,贵州省特色天然药物资源高效利用工程中心,贵州贵阳550025 [3]复旦大学药学院,上海201203 [4]贵州医科大学附属医院急诊科,贵州贵阳550004

出　　处：《中国医药工业杂志》2023年第6期937-944,共8页Chinese Journal of Pharmaceuticals

基　　金：贵州省卫生健康委科学技术基金项目(N o.gzwkj2021-463,No.gzwkj2022-230);贵州省中医药管理局中医药、民族药科学技术研究课题(No.QZYY-2021-018);贵阳市科技局(筑科合同[2020]号16-9);贵州医科大学、贵州医科大学附属医院国家自然科学基金培育项目(No.I-2020-06,No.20NSP010)。

摘　　要：该研究的目的是考察(–)-萜品-4-醇(1)在体内抗人呼吸道合胞病毒(hRSV)感染的活性。先将1和利巴韦林分别与hRSV高毒力小鼠适应株GZ08-18进行体外孵育,得到治疗组和阳性对照组的病毒株,用以感染小鼠,同时设置未经处理的病毒对照组。分别检测小鼠的体质量、存活率、肺匀浆病毒滴度、肺组织病理切片、免疫荧光强度,以及肺匀浆中炎症因子[巨噬细胞炎症蛋白-1α(MIP-1α)、白细胞介素(IL)-1α、IL-1β、IL-6和肿瘤坏死因子-α]的表达水平,以评价1的抗炎作用。结果显示,与病毒对照组相比,各治疗组小鼠的体质量回升效果显著、存活率较高、肺匀浆病毒滴度较低。病理切片的苏木精-伊红染色结果显示,治疗组与阳性对照组小鼠的肺泡结构能基本维持、肺泡间隔无增厚、未见融合;免疫荧光结果显示,各治疗组小鼠肺部的病毒蛋白表达显著降低,且肺匀浆中各炎症因子的表达水平均有所下调。其中MIP-1α和IL-1α表达下调较为显著。该研究首次报道1具有良好的体内抗hRSV感染活性。The aim of this study was to investigate the activity of(–)-terpinen-4-ol(1) against human respiratory syncytial virus(hRSV) infection in vivo.Firstly,1 and ribavirin were respectively incubated with the hRSV high-virulence strain GZ08-18.Then,the obtained strains were used to infect mice as the treatment group and positive control group.The virus control group without any treatment was set up at the same time also.Assays for evaluation of mouse body weight,survival rate,virus titers of lung tissue homogenates,pathological sections of lung tissues,immunofluorescence intensity,and detecting the expressions of macrophage inflammatory protein(MIP-1α),interleukin(IL)-1α,IL-1β,IL-6,and tumor necrosis factor-α(TNF-α) in lung homogenates were conducted to check the anti-inflammatory effect of 1.The results showed that,compared to the virus control group,all treatment groups showed better weight recovery,survival rates,and lower lung homogenate viral titers.HE staining results of pathological sections showed the alveolar structure of the mice in the treatment groups and the positive control group were maintained,the alveolar septum was not thickened,and no fusion was observed.Immunofluorescence results showed that the expressions of viral protein in lung tissues significantly decreased in the treatment groups.The expressions of inflammatory cytokines in lung homogenates were downregulated,especially the decoding of MIP-1α and IL-1α decreased remarkably.This study reported a significant effect of 1 against hRSV infection in vivo for the first time.

关 键 词：人呼吸道合胞病毒 (–)-萜品-4-醇 抗病毒药 体内研究 

分 类 号：R965[医药卫生—药理学]