[关键词]
[摘要]
目的 基于粪便代谢组学技术考察生、酒黄芩对急性肺损伤(acute lung injury,ALI)小鼠内源性代谢物的影响,并探讨黄芩酒炙"行上焦、清湿热"的作用机制。方法 小鼠口咽吸入脂多糖建立ALI模型,通过脏器指数、肺组织病理及支气管肺泡灌洗液中细胞因子水平,评价生、酒黄芩的疗效差异;采用超高效液相色谱-飞行时间质谱联用(UPLC-Q-TOF-MS)法检测内源性代谢物,运用主成分分析(principal component analysis,PCA)、正交偏最小二乘判别分析(orthogonal partial least squares discriminant analysis,OPLS-DA)等方法寻找差异性代谢物及代谢通路。结果 与对照组比较,模型组小鼠胸腺指数、脾脏指数显著降低(P<0.01),肺干湿质量比显著增加(P<0.01);支气管肺泡灌洗液中白细胞介素-6(interleukin-6,IL-6)、IL-8和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平显著升高(P<0.01),IL-10水平显著降低(P<0.01)。酒黄芩组的免疫调节及炎性反应抑制作用均显著优于生黄芩组(P<0.01)。模型组小鼠粪便中氨基酸、脂质类代谢均发生明显改变,生黄芩通过影响D-谷氨酰胺与D-谷氨酸代谢通路、鞘脂类代谢通路抑制炎性反应,酒黄芩通过影响苯丙氨酸代谢通路抑制炎性反应。结论 生、酒黄芩能够通过调节不同代谢通路抑制ALI小鼠肺部炎性反应,为阐明黄芩生熟异用的作用机制差异提供思路。
[Key word]
[Abstract]
Objective To investigate the effect of raw and wine-processed Huangqin (Scutellariae Radix) on endogenous metabolomics of mice with acute lung injury (ALI) through fecal metabolomics technology, and explore the mechanism of clearing upper-energizer dampness-heat of wine-processed Scutellariae Radix. Methods ALI mice model was established by lipopolysaccharide tracheal infusion, difference in therapeutic effect of raw and wine-processed Scutellariae Radix were evaluated by organ index, lung tissue pathology and cytokine levels in bronchial alveolar lavage fluid; UPLC-Q-TOF-MS was used to detect endogenous metabolites, principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) and other metrological methods were used to find differential metabolites and metabolic pathways. Results Compared with control group, indexes of thymus and spleen in model group were significantly decreased (P<0.01), ratio of lung dry/wet weight was significantly increased (P<0.01); Levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) in bronchial alveolar lavage fluid were significantly increased (P<0.01), and IL-10 level was significantly decreased (P<0.01). Immune regulation and inflammation inhibition effects of wine-processed Scutellariae Radix were significantly better than raw Scutellariae Radix (P<0.01). Metabolism of amino acids and lipids in model group had significantly changed, raw Scutellariae Radix alleviated inflammation by regulating D-glutamine and D-glutamate metabolism pathways and sphingolipid metabolism, wine-processed Scutellariae Radix alleviated inflammation by regulating phenylalanine metabolism pathway. Conclusion Raw and wine-processed Scutellariae Radix alleviate pulmonary inflammation in ALI mice by regulating different metabolic pathways, which provide ideas for elucidating the wine-processed mechanism of Scutellariae Radix.
[中图分类号]
R285.5
[基金项目]
江西省教育厅科技项目(GJJ201223);湖南省重点研发计划项目(2018SK2116)