胞浆识别受体NODs及其信号通路在侵袭性肺曲霉病中的作用

发布时间：2018-09-07 14:37

【摘要】：【目的】研究天然免疫系统中胞浆识别受体NODs及其信号通路在小鼠侵袭性肺曲霉病(IPA)中的作用。【方法】小鼠随机分为正常对照组、正常+接种烟曲霉菌组(正常感染组)和免疫抑制+接种烟曲霉菌组(IPA组),经鼻吸入烟曲霉孢子后在不同时相点处死小鼠,无菌取肺组织分别进行病理切片,烟曲霉菌落计数,RT-PCR法、Western blot法动态检测小鼠感染烟曲霉菌过程中肺组织NOD1、NOD2、RIP2 mRNA表达,促炎细胞因子TNF-α含量的变化规律。【结果】鼻吸入烟曲霉菌后72 h时,IPA组肺组织出现严重炎症反应,并有大量的菌丝生成,同时各时相点的烟曲霉菌负荷均高于正常感染组;与正常感染组比较,IPA组NOD1、RIP2 mRNA持续低表达,而NOD2 mRNA则在感染最早期(24 h)异常高表达,而在随后的感染过程中一直处于低表达状态;正常小鼠感染烟曲霉菌后,肺组织中促炎细胞因子TNF-α在感染前期皆呈高表达,且最高表达量均出现在48 h或72 h,之后下降并恢复至正常水平。而IPA小鼠促炎症细胞因子TNF-α缓慢且低水平释放。【结论】NOD1、RIP2的表达受到长期抑制,NOD2在感染最早期的过度激活以及随后的抑制表达,引起促炎细胞因子低表达,可能导致了侵袭性肺曲霉的发生发展。
[Abstract]:[objective] to study the role of cytoplasmic recognition receptor (NODs) and its signal pathway in murine invasive pulmonary aspergillosis (IPA) in innate immune system. [methods] mice were randomly divided into normal control group. Normal inoculated aspergillus fumigatus group (normal infection group) and immunosuppressive inoculated aspergillus fumigatus group (IPA group). After nasal inhalation of aspergillus fumigatus spores, the mice were killed at different time points. The expression of NOD1,NOD2,RIP2 mRNA in lung tissue of mice infected with Aspergillus fumigatus was detected by RT-PCR and Western blot. [results] at 72 h after nasal inhalation of Aspergillus fumigatus, severe inflammatory reaction occurred in lung tissue and a large amount of mycelium was produced in IPA-treated group, and the load of Aspergillus fumigatus at each time point was higher than that in normal infection group. Compared with the normal infection group, the expression of NOD1,RIP2 mRNA in the IPA group continued to be low, while the expression of NOD2 mRNA was abnormally high in the early stage of infection (24 h), and remained in a low expression state during the subsequent infection, and the normal mice were infected with Aspergillus fumigatus. The expression of proinflammatory cytokine TNF- 伪 in lung tissue was high in the preinfection stage, and the highest expression occurred at 48 h or 72 h, then decreased and returned to normal level. However, IPA mice promote the slow and low release of inflammatory cytokine TNF- 伪. [conclusion] the expression of NOD1,RIP2 was inhibited by the excessive activation of NOD2 in the early stage of infection and the subsequent inhibition of the expression of NOD1,RIP2, which resulted in the low expression of proinflammatory cytokines. This may lead to the development of invasive pulmonary aspergillus.
【作者单位】：江西中医学院现代中药制剂教育部重点实验室;湖南中医药大学药学院;江西中医学院药学院;南昌大学医学院微生物学教研室;
【基金】：国家自然科学基金项目(No.30560147,30760236)
【分类号】：R563

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