小鼠侵袭性肺曲霉病发病过程中TLRs/NF-κB信号通路的激活  

The activation of TLRs/NF-κB signal pathways in the invasive pulmonary aspergillosis of mice

作　　者：李祥[1] 罗闳丹[1] 石青[2] 谢小梅[1] 刘金辉[2] 

机构地区：[1]江西中医学院现代中药制剂教育部重点实验室,南昌330004 [2]南昌大学医学院微生物学教研室,南昌330006

出　　处：《中国免疫学杂志》2010年第10期881-884,共4页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(30560147和30760236)

摘　　要：目的:研究小鼠侵袭性肺曲霉病(IPA)发生过程中TLRs/NF-κB信号通路的激活,探讨IPA的发病机理。方法:小鼠随机分为正常组(N)、正常接菌组(N+Af)和IPA模型组(IPA),经鼻吸入烟曲霉(Af)孢子后在不同时相点处死小鼠,无菌取肺组织行病理切片、Af菌落计数,RT-PCR法检测TLR2和TLR4 mRNA、蛋白印迹法检测NF-κBp65、IL-1β的表达。结果:(1)鼻吸入Af后72小时时,IPA组肺组织出现严重炎症反应,并有大量的菌丝生成,同时各时相点的菌负荷均高于N+Af组;(2)与N+Af组比较,IPA组TLR2 mRNA后期异常高表达,TLR4 mRNA持续低表达,NF-κBp65早期骤然升高后又持续下降,IL-1β一直呈低表达状态。结论:TLRs的异常激活导致宿主下游信号的低反应性,宿主不能清除Af促使了IPA的发生发展。Objective： To study the activation of TLRs/NF-κB signal pathway in Invasive Pulmonary Aspergillosis.Methods： The mice were randomly selected into three groups：the normal mice（N）, the normal mice with infection（ N ＋ Af） and IPA mice（IPA）. The mice were administrated with Aspergillus fum/gatus （Af） via intranasal and sacrificed at different time. The lung tissue of mice were extracted under sterile condition, and then studied by pathological section, counting the lung burden and detecting the expression of the TLR2, TLR4 mRNA by RT- PCR,NF-κB and IL-1β with the Western blot. Results： 72hs later after infection, IPA mice were serious inflammatory reaction and hypha appeared, also lung burdem was higher than in N mice. Compared to the N ＋ M mice, TLR2 mRNA of IPA mice were high expression abnormally at late time with, persistent low expression TLR4 mRNA, and NF-κB 1365 increased sharply early and then decreased persistently, IL-1β was in low expression. Conclusion： The abnormally activation of TLRs/NF-κB induces low action of the doffustream, so hosts can＇t clear the Aspergillus fumigatus which results in the development of IPA.

关 键 词：TLR/NF-κB 侵袭性肺曲霉病 AF 天然免疫 模式识别受体 

分 类 号：R341[医药卫生—基础医学]