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[摘要]
目的 筛选甲型H1N1流感病毒性肺炎小鼠肺组织中疾病相关差异性代谢物,观察蒲地蓝消炎口服液对肺炎小鼠代谢物的调控作用,探讨其治疗病毒性肺炎的作用机制。方法 将ICR小鼠随机分为对照组、模型组、蒲地蓝组和利巴韦林组(n=10),以H1N1病毒尿囊液滴鼻造模。蒲地蓝组和利巴韦林组小鼠每日ig给药1次,连续用药6 d,末次给药后2 h处死并收集肺组织样本。采用基于GC-MS的代谢组学技术分析各组小鼠肺组织样本中代谢物的变化,综合P<0.05、VIP>1.0、Fold Change>1.5条件筛选H1N1流感病毒性肺炎的疾病生物标志物。通过代谢通路富集分析初步探讨蒲地蓝消炎口服液治疗病毒性肺炎的作用机制。结果 H1N1病毒感染导致小鼠肺部炎性细胞浸润及不同程度的肺炎,多种代谢物代谢紊乱,蒲地蓝消炎口服液及利巴韦林均能改善肺炎症状,并对多种代谢物起到回调作用。结论 蒲地蓝消炎口服液主要通过调节机体内14个代谢物及12条相关代谢通路发挥治疗甲型H1N1流感病毒性肺炎的作用。
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[Abstract]
Objective To screen the pneumonia-related abnormal metabolites in lung tissue of mice infected by Influenza A/H1N1, and to monitor the regulation effect of Pudilan Xiaoyan Oral Liquid and to explore potential anti-pneumonia mechanism.Methods ICR mice were randomly divided into four groups with ten mice in each group:normal group, model group, Pudilan group, and Ribavirin group. The mice were infected with H1N1 virus intranasally and gavage once every-day for six consecutive days. 2 h after the last dose, the mice were sacrificed and lungs were collected. Metabolomics based on GC-MS was applied to analyze the changes of metabolites in the lung tissue of each group. The potential biomarkers of H1N1-induced pneumonia were screened by three conditions:P < 0.05, VIP > 1.0, and Fold Change > 1.5. Metabolic pathways related to the treatment mechanism of Pudilan Xiaoyan Oral Liquid were analyzed.Results The infection of H1N1 virus leads to infiltration of inflammatory cells in the lungs of mice and various degrees of pneumonitis and metabolic disorders. Pudilan Xiaoyan Oral Liquid and ribavirin can both ameliorate the symptoms of pneumonia and play role in callback of various metabolites.Conclusion The treatment effect of Pudilan Xiaoyan Oral Liquid on H1N1-induced pneumonia is related to the regulation effects on 14 potential biomarkers and 12 associated metabolic pathways.
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[基金项目]
江苏省"333工程"科研项目(BRA2016427);江苏省"六大人才高峰"高层次人才选拔培养资助项目(YY-022);江苏省高校中医学优势学科建设工程资助项目(PAPD)