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【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。
【Aim】 To study the role of cytoplasmic recognition receptors (NODs) and their signaling pathways in the development of mouse invasive pulmonary aspergillosis (IPA) in the innate immune system. 【Methods】 The mice were randomly divided into normal control group, normal + vaccinated group of Aspergillus fumigatus (normal infection group) and immunosuppressive + vaccinated group of Aspergillus fumigatus (IPA group). After inhaled aspergillus fumigatus spores at different time points The mice were sacrificed and the aseptic lungs were taken for pathological section, Aspergillus fumigatus colony counting, RT-PCR and Western blot respectively to detect the expression of NOD1, NOD2 and RIP2 mRNA in lung tissue of mice infected with Aspergillus fumigatus, Factor TNF-α content of the law. 【Results】 The lungs of IPA group developed severe inflammatory reaction at 72 h after inhalation of Aspergillus Fumigatus, and a large amount of mycelium was formed. At the same time, the Aspergillus fumigatus burden in IPA group was higher than that in normal infection group. In contrast, NOD1 and RIP2 mRNA in IPA group continued to be low, while NOD2 mRNA was abnormally high in the early stage of infection (24 h), and remained low during the subsequent infection. After normal mice were infected with Aspergillus fumigatus The expression of TNF-α in lung tissue was high in the early stage of infection, and the highest expression level appeared in 48 h or 72 h, then decreased and returned to normal level. While the IPA mouse pro-inflammatory cytokine TNF-α released slowly and at low levels. 【Conclusion】 The expression of NOD1 and RIP2 were inhibited for a long time. NOD2 overexpression and subsequent suppression in the early stage of infection led to the low expression of proinflammatory cytokines, which may lead to the development of invasive pulmonary fungus.