基于代谢组学探究痛泻要方干预胃溃疡肝郁脾虚证的作用机制
Mechanism of Tongxie Yaofang on gastric ulcer with liver-depression and spleen-deficiency syndrome based on metabolomics
章嘉祺 1余王琴 1宋红 1汪桂岳 1侯欣 1沈琰 1郭祥 1陈家昊1
作者信息
- 1. 浙江中医药大学基础医学院,杭州 310053
- 折叠
摘要
目的:利用非靶向代谢组学技术,研究痛泻要方对肝郁脾虚证胃溃疡大鼠粪便代谢的影响和潜在的作用机制.方法:SD大鼠随机分为空白对照组、模型组、痛泻要方组,每组6只,灌胃给药.采用多因素复合模拟中医病因结合乙酸注射法复制肝郁脾虚证胃溃疡大鼠模型.通过大鼠胃窦组织病理检测,血清病理生化指标含量,Western Blot实验,超高效液相色谱-四极杆-飞行时间质谱法等,结合人类代谢组数据库(HMDB)和基因组数据库(KEGG)与MetaboAnalyst 5.0,分析生物标志物的相应代谢通路及通路富集和相关蛋白的表达水平的影响.结果:痛泻要方能够降低血清中NE、5-HT的水平(P＜0.01),而升高血清中GAS、D-木糖水平(P＜0.01),显著下调p-PI3K/PI3K蛋白表达(P＜0.01),上调p-Akt1/Akt1蛋白表达(P＜0.01),同时痛泻要方可以缓解肝郁脾虚证胃溃疡对大鼠胃黏膜造成的病理损伤.筛选共19种差异最为显著的潜在生物标志物,涉及氨基酸代谢、能量代谢和脂类代谢等主要差异代谢通路.结论:痛泻要方能够减轻胃肠道炎症反应,缓解肝郁脾虚证胃溃疡模型大鼠的病理进程,通过调节氨基酸代谢、能量代谢和脂类代谢,抑制炎症反应和氧化应激促进大鼠胃黏膜组织的修复.
Abstract
Objective:To investigate the effects of Tongxie Yaofang(TXYF)on fecal metabolism and the potential mechanism of action in rats with liver-depression and spleen-deficiency syndrome of gastric ulcer using non-targeted metabolomics.Methods:SD rats were randomly divided into blank control group,model group and TXYF group,with 6 rats in each group,and the drugs were administered by gavage.A multifactorial composite simulation of Chinese medicine etiology combined with acetic acid cauterization was used to replicate the rat model of gastric ulcer with liver depression and spleen deficiency syndrome.By histopathologic detection of gastric sinus,serum pathological and biochemical index levels,Western Blot(WB)experiments,ultra-high performance liquid chromatography(UPLC)-quadrupole-time-of-flight mass spectrometry(UPLC-TOF-MS),etc.,combined with the Human Metabolome Data Bank(HMDB)and the Genome Data Bank(KEGG)with MetaboAnalyst 5.0,to analyze the corresponding metabolic pathways of the biomarkers and the pathway enrichment and expression levels of related proteins.Results:TXYF was able to reduce the serum levels of NE and 5-HT(P＜0.01),and increase the serum levels of GAS and D-xylose(P＜0.01),and significantly decreased the protein expression of p-PI3K/PI3K(P＜0.01),and up-regulated the protein expression of p-Akt1/Akt1(P＜0.01),and at the same time,TXYF was able to alleviate the pathological damage caused by the gastric mucosa of the rat gastric ulcer in the syndrome of liver-depression and spleen-deficiency.A total of 19 potential biomarkers with the most significant differences were screened,involving major differential metabolic pathways such as amino acid metabolism,energy metabolism and lipid metabolism.Conclusion:TXYF can reduce gastrointestinal inflammatory reaction,alleviate the pathological process of gastric ulcer model rats with liver-depression and spleen-deficiency,and promote the repair of gastric mucosal tissues by regulating amino acid metabolism,energy metabolism and lipid metabolism,and inhibiting inflammatory reaction and oxidative stress.
关键词
痛泻要方/肝郁脾虚证/胃溃疡/非靶向代谢组学/氨基酸代谢Key words
Tongxie Yaofang/Liver-depressing and spleen-deficiency syndrome/Gastric ulcer/Non-targeted metabolomics/Amino acid metabolism引用本文复制引用
基金项目
浙江省基础公益项目联合基金(LBY21H270002)
浙江省基础公益项目联合基金(LGF20H270013)
出版年
2024
NETL
NSTL
万方数据