猪胸膜肺炎放线杆菌感染小鼠所致炎症中TLR-4信号通路涉及细胞焦亡  

TLR-4 involvement in pyroptosis of mice with pulmonary inflammation infected by Actinobacillus pleuropneumoniae

作　　者：胡佩佩[1] 黄复深[1] 牛俊超[1] 唐昭山[1] 

机构地区：[1]湖南农业大学动物医学院,湖南长沙410128

出　　处：《微生物学报》2015年第5期650-656,共7页Acta Microbiologica Sinica

基　　金：湖南农业大学校研究生创新课题(12254-YCX201302);教育部留学回国科研启动基金(GT0096)~~

摘　　要：【目的】探讨革兰氏阴性菌胸膜肺炎放线杆菌(Actinobacillus Pleuropneumoniae,APP)感染小鼠致肺病变的分子细胞机制,以改善猪传染性胸膜肺炎的防治。【方法】滴鼻法感染小鼠,观察肺部眼观病变,石蜡切片HE染色观察肺组织病变。RT-PCR和q PCR方法检测小鼠肺部的Caspase-1、Caspase-3、TNF-α、IL-1β、IL-6、IL-18、TLR-4表达量的变化。【结果】小鼠在感染后48h内死亡,解剖后观察小鼠肺部有严重出血和炎症。实验组小鼠肺组织IL-1β、IL-6、IL-18和TNF-α的表达水平显著增加;TLR-4的表达量显著上调;肺部组织Caspase-1的表达水平明显升高,而Caspase-3的表达水平未见明显变化。【结论】TLR-4信号通路可能参与APP感染引起的肺部炎症的发生,APP感染后激活TLR-4信号通路使有关细胞释放炎症因子,引起的肺部炎症。炎症可能涉及Caspase-1参与的细胞焦亡。[ Objective] Pyroptosis is a caspase-1 dependent programmed cell death and involves pathogenesis of infectious diseases by releasing many pro-inflammatory cytokines to induced inflammation. TLR--4 plays an important role in mediating pathogenesis of some infectious diseases. In this study, we detected the expression of TLR-4 and some molecules （e. g caspase-1, TNFα, IL-1β, IL-6, IL-18） related with pyroptosis to determine its involvement and mechanisms of pulmonary inflammation in mice infected by A. pleuropneumoniae. [ Methods ] Mice were intranasally infected by A. pleuropneumoniae and killed 48 hours post infection. Pulmonary gross lesion and histological pathology by H-E were observed. Expression levels of caspase-1, caspase-3, TNF-α, IL-1β, IL-6, IL-18, and TLR-4 in tung of mice were detected by RT-PCR and qPCR. [ Results] Serious pulmonary hemorrhage and inflammation in infected mice were observed. Expression levels of caspase-1, caspase-3, TNF-α, IL-1β, IL-6, IL-18 and TLR-4 increased, and expression levels of caspase-3 were not changed in lung of infected mice. [ Conclusion ] TLR-4 might be involved in pulmonary inflammation of mice infected by A. pleuropneumoniae. After induced by activated TLR-4 some cells in this lesion expressed pro-inflammatory cytokines. These cytokines would induce pulmonary inflammation. This lesion might involve pyroptosis with caspase-1 expression.

关 键 词：猪传染性胸膜肺炎 小鼠 病理学 分子和细胞机制 TLR-4信号通路 细胞焦亡 

分 类 号：S858.28[农业科学—临床兽医学]