基于非靶标血清代谢组学研究桔梗预防急性肺损伤的潜在作用机制

目的  基于非靶标血清代谢组学探讨桔梗预防急性肺损伤(ALI)小鼠的潜在作用机制。方法  24只C57BL/6J小鼠随机分为空白组、模型组、阳性药(地塞米松)组和桔梗组, 每组6只。给药干预7 d后, 除空白组外, 其余小鼠气管滴注脂多糖(LPS)3 mg·kg-1建立ALI模型, 测定各组小鼠的肺组织病理和炎性因子水平的表达情况; 收集小鼠血清, 采用GC-MS技术对血清样本进行质谱检测, 应用PCA进行血清代谢轮廓的比较, 运用Metaboanalyst 5.0分析相关代谢通路。结果  与空白组相比, 模型组的肺部病理情况严重, 炎性因子水平显著升高(P < 0.05), 阳性药组和桔梗组较模型组小鼠的肺组织病理有一定的改善, 炎性因子水平明显降低(P < 0.01)。血清代谢组学结果显示: 空白组和模型组的代谢轮廓具有明显的差异, 阳性药组和桔梗组的代谢轮廓趋近正常组。结论  桔梗对ALI小鼠的炎症有一定的改善作用, 其潜在作用机制可能与回调多种血清代谢物的含量及调控多条代谢通路相关。 

Potential Mechanism of Platycodon Grandiflorum in the Prevention of Acute Lung Injury Based on Non-Target Serum Metabolomics

OBJECTIVE  To investigate the potential mechanism of platycodon grandiflorum in preventing acute lung injury in mice based on non-target serum metabolomics.METHODS  Twenty-four C57BL/6J mice were randomly divided into control, model, positive and platycodon grandiflorum groups. After 7 days of drug intervention, except for the control group, the other mice were injected with lipopolysaccharide (3 mg·kg-1) to establish the acute lung injury model and the lung pathology and the expression of inflammatory factors in each group were determined. The serum of mice was collected, and the serum samples were detected by mass spectrometry using GC-MS. The serum metabolic profiles were compared by PCA and Metaboanalyst 5.0 was used to analyze related metabolic pathways.RESULTS  Compared with the control group, the lung pathology of the model group was serious, and the inflammatory factors significantly increased (P < 0.05). Compared with the model group, the pathological conditions of the positive and platycodon grandiflorum groups were improved to some extent, and the inflammatory factors were significantly reduced (P < 0.01). Serum metabolomics results showed that the metabolic profile of the control group and the model group was significantly different, and the metabolic profiles of the positive and platycodon grandiflorum group were close to the normal group.CONCLUSION  Platycodon grandiflorum can improve the inflammation in acute lung injury mice, its potential mechanism may be related to the callback variety of the content of serum metabolites and control multiple metabolic pathways.