摘要
为了阐明荆防颗粒治疗急性肺损伤的效果及作用机制,并考察荆防颗粒对急性肺损伤粪便内源性代谢物代谢紊乱和肠道菌群稳态的调控作用,将小鼠随机分为假手术组、模型组、荆防颗粒组,造模后持续给药6 d。利用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱联用仪(UHPLC-HESI-QE-Orbitrap-MS/MS)代谢组学技术和16S rRNA高通量测序技术,测定小鼠肠道中内源性小分子物质和肠道菌群的变化,并寻找出潜在的生物标志物。结果显示,荆防颗粒可以对11个生物标志物L-谷氨酸、琥珀酸、花生四烯酸、亚油酸、亚麻酸、苯丙氨酸、鞘氨醇、丁酸、丙酮酸、色氨酸、棕榈酸进行调控。对这11个生物标志物通过在线软件MetaboAnalyst进行代谢通路分析,得到潜在的主要代谢通路,其中共有10条代谢通路与荆防颗粒治疗急性肺损伤密切相关,包括丙氨酸、天门冬氨酸和谷氨酸代谢,氨基酰基tRNA生物合成,三羧酸循环,乙醛酸及二羧酸代谢,精氨酸和脯氨酸代谢,亚油酸和亚麻酸代谢,氮代谢,谷氨酰胺和D-谷氨酸代谢,苯丙氨酸、酪氨酸和色氨酸的生物合成,苯丙氨酸代谢。肠道菌群结果显示显著性差异菌主要有Bacteroides、Akkermansia、Lachnospiraceae_NK4A136_group、Lachnoclostridium和Klebsiella。Spearman分析证实,Akkermansia、Lachnospiraceae_NK4A136_group与琥珀酸、花生四烯酸、亚麻酸、亚油酸、丁酸、丙酮酸丰度呈显著正相关;Bacteroides、Klebsiella、Lachnoclostridium与L-谷氨酸、苯丙氨酸、鞘氨醇丰度呈显著正相关。以上结果表明荆防颗粒治疗急性肺损伤作用是通过改善急性肺损伤小鼠肠道菌群失调,与平衡丙氨酸、天门冬氨酸和谷氨酸代谢,氨基酰基tRNA生物合成,三羧酸循环,苯丙氨酸、酪氨酸和色氨酸的生物合成,亚油酸代谢等通路来实现的。
This study aims to elucidate the therapeutic effect and mechanism of Jingfang Granules on acute lung injury,and to investigate the regulatory effect of Jingfang Granules on the metabolic disorders of endogenous metabolites in feces and the homeostasis of intestinal microbiota in acute lung injury,mice were randomly divided into a sham group,a model group,and a Jingfang Granules group.After modeling,the mice were continuously administered for 6 days.Using ultra-high performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry(UHPLC-HESI-QE-Orbitrap-MS/MS)metabolomics technology and 16S rRNA high-throughput sequencing technology,changes in endogenous small molecule substances and gut microbiota in mouse intestines were determined,and potential biomarkers were identified.The results showed that Jingfang Granules can regulate 11 biomarkers,including L-glutamic acid,succinic acid,arachidonic acid,linoleic acid,linolenic acid,phenylalanine,sphingosine,2-hydroxy-2-methyl butyric acid,pyruvate,tryptophan,and palmitic acid.Metabolic pathway analysis was conducted on these 11 biomarkers using the online software MetaboAnalyst,identifying potential major metabolic pathways.Among them,a total of 10 metabolic pathways are closely related to the treatment of acute lung injury with Jingfang Granules,including alanine,aspartate and glutamate metabolism,aminoacyl-tRNA biosynthesis,citrate cycle(TCA cycle),alyoxylate and dicarboxylate metabolism,arginine and proline metabolism,linoleic acid metabolism and linolenic acid metabolism,nitrogen metabolism,D-glutamine and D-glutamatemetabolism,phenylalanine,tyrosine and tryptophan biosynthesis,phenylalanine metabolism.The results of gut microbiota showed significant differences in bacteria,mainly including Bacteroides,Akkermansia,Lachnospiraceae_NK4A136_group,Lachnochlostridium,and Klebsiella.Spearman analysis confirms that Akkermansia and Lachnospiraceae_NK4A136_group is a significant positive correlation between the abundance of succi
作者
肖贺
孙兴旭
孙成宏
王恩力
王现珍
姚景春
XIAO He;SUN Xing-xu;SUN Cheng-hong;WANG En-li;WANG Xian-zhen;YAO Jing-chun(State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine,Lunan Pharmaceutical Group Co.,Ltd.,Linyi 276006,China;Center for New Drug Pharmacology,Lunan Pharmaceutical Group Co.,Ltd.,Linyi 273400,China;Guangdong Pharmaceutical University,Guangzhou 510006,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2024年第7期1915-1923,共9页
China Journal of Chinese Materia Medica
基金
山东省自然科学基金创新发展联合基金项目(ZR2022LZY021)。
关键词
荆防颗粒
急性肺损伤
代谢组学
肠道菌群
代谢通路
Jingfang Granules
acute lung injury
metabolomics
intestinal flora
metabolic pathway
