中文摘要：

【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、Westernblot法动态检测小鼠感染烟曲霉菌过程中肺组织NOD1、NOD2、RIP2mRNA表达，促炎细胞因子TNF-Ⅱ含量的变化规律。【结果】鼻吸入烟曲霉菌后72h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、RIP2mRNA持续低表达，而NOD2mRNA则在感染最早期（24h）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48h或72h，之后下降并恢复至正常水平。而IPA小鼠促炎症细胞因子TNF-Ⅱ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。

英文摘要：

[Objective] To study the role of the nucleotide binding oligomerization domain-like receptor （NODs） and their signaling pathways in the pathogenesis of invasive pulmonary aspergillosis （IPA） in mice. [Methods] Mice were randomly divided into three groups： negative control, mice infected with Aspergillus fumigatus only and mice of combination of immunosuppression and Aspergillus fumiga- tusinfection （IPA group）. Only IPA mice were immunosuppressed with Cyclophosphamide （100 mg/d） for 2 d before Aspergillus fumigatus spores were inhaled into mice of different groups, normal saline was used instead for negative control. Then mice were killed at different time points and lung tissues were collected for biopsy and Aspergillusfumigatus colony count. RT-PCR and Western blot were used to measure NOD1, NOD2, RIP2 mRNA level and TNF-α protein expression in lung tissues, respec- tively. [Results] At 72 h of post-infection, severe inflammation and a large number of hyphae were ob- served in lung tissues of IPA mice. Their Aspergillusfumigatus load at all time points were higher when compared with mice infected with Aspergillusfumigatus only, and their NOD1 and RIP2 mRNA levels were continuously lower. While NOD2 mRNA was abnormally highly expressed at 24 h and stayed at low expression level afterwards. TNF-α was highly expressed in mice infected with Aspergillus fumi- gatus only and reached the peak at 48 h and 72 h post-transfection. However, TNF-α was released slowly and lowly in IPA mice. [Conclusion] Persistently inhibited NOD 1 and RIP2 expression along with late-stage inhibited NOD2 expression in IPA mice resulted in the low-expression of proinflamma- tory cytokine, which may led to the development of invasive pulmonary aspergillosis.