肠道菌群失调对流感病毒感染小鼠急性肺损伤的影响

目的 探讨肠道菌群失调对流感病毒感染小鼠急性肺损伤的影响及作用机制。方法 BALB/c小鼠随机分为正常对照组、流感病毒对照组、甲硝唑模型组，每组12只。甲硝唑模型组小鼠用甲硝唑（18 mg/mL）连续灌胃8 d，于d9滴鼻甲型流感病毒A/PR/8/4稀释液（103pfu/鼠），构建肠道菌群失调小鼠感染流感病毒的模型。观察各组小鼠肺组织及盲肠的病理变化，检测肺组织中脂多糖LPS及炎性相关因子肿瘤坏死因子 - α（Tumor necrosis factor - α，TNF - α）、白介素 - 1β（Interleukin - 1β, IL - 1β）、白介素 - 6（Interleukin - 6，IL - 6）、干扰素 - β（Interferon - β，IFN - β）水平，并采用免疫组织化学染色法定位肺组织Toll样受体4（Toll - like receptor 4, TLR4）表达情况。结果 甲硝唑模型组小鼠肺及盲肠组织炎症损伤和病理改变情况较比病毒对照组更加严重，同时小鼠肺组织中LPS含量显著增加，差异有统计学意义（P＜0.05），TNF - α、IL - 1β、IL - 6、IFN - β水平明显升高（P＜0.05）。TLR4在甲硝唑模型组小鼠肺组织中的表达明显高于病毒对照组，差异有统计学意义（P＜0.05）。结论 肠道菌群失调引起LPS/TLR4通路激活，从而上调小鼠肺组织流感病毒所致的炎性风暴，进一步加重流感病毒引起的组织病理改变。

Effect of intestinal flora imbalance on acute lung injury in mice infected with influenza virus

Objective The aim of this study was to investigate the effect and mechanism of intestinal flora imbalance on acute lung injury in mice infected with influenza virus. Methods The BALB/c mice were divided into normal control group, influenza virus control group and metronidazole model group with 12 mice in each group. Metronidazole model group was treated with metronidazole(18 mg/mL) for 8 days in order to construct the model of intestinal flora imbalance. Then the mice were infected with influenza virus A/PR/8/4 (103 pfu/mouse) by intranasal instillation to construct the model of influenza virus infection on day 9. The pathological changes of lung tissue and cecum were observed. The levels of lipopolysaccharide (LPS) and inflammatory cytokine of TNF-α, IL-1, IL-6 and IFN-β in lung tissue were detected. The expression of TLR4 in lung tissue was determined by immunohistochemistry. Results Compared with the virus control group, the tissue of lung and cecal in metronidazole model group showed more severe inflammatory injury, while the content of LPS in lung tissue increased significantly (P<0.05). The level of TNF-α, IL-1β, IL-6, IFN-β level were significantly increased (P<0.05). The location of TLR4 in the metronidazole model group was significantly higher than that in the virus control group (P<0.05). Conclusion Intestinal flora imbalance activated LPS/TLR4 pathway, then up-regulated inflammatory storm caused by influenza virus infection, and further aggravated the histopathological changes in lung tissue of mice infected influenza virus.