NF-κB启动的炎症反应在小鼠侵袭性肺曲霉病肺损伤中的作用

The Effect of Inflammation-mediated by NF-κB on Lung Injury of Mice with Invasive Pulmonary Aspergillosis

摘要:

为了探讨NF-κB启动的炎症反应在小鼠侵袭性肺曲霉病肺损伤中的作用, 将小鼠分3组:正常组、正常+烟曲霉菌接种组、IPA模型组, 小鼠鼻吸入烟曲霉菌第4天处死, 取肺组织, 肺组织切片经HE染色观察病理损伤; 比色法测定肺组织MPO活性; 免疫组化法评价肺组织NF-κB p65蛋白的活化; RT-PCR法检测肺组织TNF-α、IFN-γ和β-tublin mRNA的表达。 结果显示, 正常健康组小鼠肺组织结构正常, 未见炎症发生; 正常+烟曲霉菌接种组小鼠肺组织有炎症细胞浸润, 未见孢子萌芽; IPA模型组小鼠的肺组织病理损伤严重, 可见炎症细胞浸润, 孢子萌芽生成菌丝。正常+烟曲霉菌接种组和IPA模型组小鼠肺组织的TNF-a和IFN-γmRNA的相对表达水平、NF-κB p65免疫组化评分和MPO活性均高于正常组小鼠(P<0.05); 并且IPA模型组小鼠肺组织NF-κB p65免疫组化评分值和MPO活性均高于正常+烟曲霉菌接种组(P<0.05)。结果提示, 烟曲霉菌感染可激活小鼠肺组织NF-κB介导的炎症信号通路, 诱导下游TNF-a和IFN-γ的表达, 募集大量的中性粒细胞于感染组织, 是导致IPA小鼠肺组织严重病理损伤的因素之一。

Abstract:

The aim of this study was to explore the effect of inflammation-mediated by NF-κB on lung injury of mice with invasive pulmonary aspergillosis. The mice were divided into three groups including the group of normal mice, the group of normal mice with infection and the group of IPA mice. The mice were sacrificed on day 4 post-infection. The lung tissues from each group were collected for observing the pathological alteration, evaluating histological scores of NF-κB p65 with immuno-histochemistry stain, detecting mRNA expression level of TNF-α and IFN-γ in comparison to β-tublin in ratio of densitometric units using RT-PCR and measuring MPO of neutrophils with colorimetry. The pathological analysis showed the normal structure and no inflammatory reaction in the lungs of the normal mice; and the infiltration of inflammatory cells, weak injury and no germination of spore into hypha in the lungs of normal mice infected with A. fumigatus and serious injury like destruction of alveolar structure, bleeding and germination of spore into hypha in the lungs of IPA mice. The expression level of TNF-a and IFN-γ, histological score of NF-κB p65 and activity of MPO in both groups of normal mice infected with A. fumigatus and IPA were higher than in the normal mice group(P<0.05). But histological score of NF-κB p65 and activity of MPO in IPA mice were higher than in normal mice infected with A. fumigatus(P<0.05). The results suggested that the expression of TNF-a and IFN-g as well as recruitment of neutrophils that were promoted by the signal pathway mediated by NF-κB activated by infection of A. fumigatus may be one of the factors that cause the seriously pathological injury of lungs in the mice with invasive pulmonary aspergillosis.