基于代谢组学探讨酒煨大黄缓和“损胃气”的机制  

Metabolomics Reveals the Mechanism of Rice Wine-Simmered Dahuang(大黄) in Alleviating Sunweiqi(损胃气)

作　　者：李振辉 王本业 陈思妙 王琦 涂济源 周仲实 王光忠 LI Zhenhui;WANG Benye;CHEN Simiao;WANG Qi;TU Jiyuan;ZHOU Zhongshi;WANG Guangzhong(School of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065;Hubei Engineering Technology Research Center of Traditional Chinese Medicine Processing,Wuhan 430065)

机构地区：[1]湖北中医药大学药学院,武汉430065 [2]湖北省中药炮制工程技术研究中心,武汉430065

出　　处：《中药药理与临床》2025年第1期100-105,123,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家中医药管理局资助项目(国中医药科技中药便函[2022]59号)。

摘　　要：目的:探讨大黄酒煨前后对正常小鼠胃肠功能的作用差异及其机制。方法:将ICR小鼠随机分为正常对照组、生大黄3、12 g/kg组、酒煨大黄3、12 g/kg组。每天观察小鼠体质量和腹泻指数;给药7 d后,检测胃内容物残留率和小肠推进率,并进行胃HE切片染色;酶联免疫吸附法检测血清中MTL、GAS含量;RT-qPCR法检测胃组织中Tnfa、Il6、Il1b的mRNA表达;通过气相色谱质谱联用仪(GC-MS)筛选差异代谢物,并进行代谢通路富集分析。结果:与正常对照组比较,生大黄、酒煨大黄3、12 g/kg组给药3 d后体质量显著降低(P<0.01),生大黄3、12 g/kg组、酒煨大黄12 g/kg腹泻指数明显升高(P<0.05或P<0.01),各给药组胃内容物残留率增加,小肠推进率降低,血清MTL、GAS含量降低,生大黄12 g/kg组炎症因子mRNA表达明显上调(P<0.01)。相较于生大黄组,酒煨大黄组小鼠体质量显著升高、腹泻指数降低、胃内容残留率降低、小肠推进率及胃肠激素提高、炎症因子mRNA表达下调、胃组织炎性浸润减轻、差异代谢物D-半乳糖、D-葡萄糖、D-果糖、胆钙化醇的水平降低,肌醇、花生四烯酸、棕榈酸的水平增加(P<0.05或P<0.01)。结论:酒煨大黄较生大黄能缓和胃肠道不良反应,其机制可能与调节半乳糖代谢途径有关。该结果为进一步阐释酒煨大黄减轻“损胃气”副作用提供依据。Objective:To compare the effects and mechanisms of raw and rice wine-simmered Dahuang(大黄) in regulating the gastrointestinal function in normal mice. Methods:ICR mice were randomly grouped as follows: blank, high-and low-dose(12 g/kg and 3 g/kg, respectively) raw Dahuang, and high-and low-dose(12 g/kg and 3 g/kg, respectively) rice wine-simmered Dahuang. The body weight and diarrhea index of mice were measured daily. After 7 days of administration, the gastric residual volume and small intestinal propulsion rate were determined, and the gastric tissue was stained with hematoxylin-eosin. Enzyme-linked immunosorbent assay was employed to measure the levels of motilin and gastrin in the serum. RT-qPCR was used to determine the mRNA levels of tumor necrosis factor-alpha, interleukin-6,and interleukin-1 beta in the gastric tissue. Differential metabolites were screened by gas chromatography-mass spectrometry, and metabolic pathway enrichment analysis was carried out. Results:Compared with normal group, raw Dahuang and rice wine-simmered Dahuang groups significantly decreased the body weight after 3 days of administration(P<0.01), raw Dahuang 12 g/kg and 3 g/kg groups and rice wine-simmered Dahuang 12 g/kg group significantly increased the diarrhea index(P<0.05 or P<0.01), all raw Dahuang and rice wine-simmered Dahuang groups increased the gastric residual volume, reduced the small intestinal propulsion rate, motilin, and gastrin, the raw Dahuang 12 g/kg group elevated the mRNA expression of pro-inflammatory cytokines(P<0.01). Compared with raw Dahuang groups, rice wine-simmered Dahuang groups significantly increased the body weight, reduced the diarrhea index and gastric residual volume, increased the small intestinal propulsion rate and gastrointestinal hormones, lowered the mRNA expression of pro-inflammatory cytokines, reduced inflammatory infiltration, and decreased the differential metabolites D-galactose, D-glucose, D-fructose, and cholecalciferol, and increased inositol, arachidonic acid, and palmitic acid(

关 键 词：大黄 黄酒煨制 胃肠功能 代谢组学 炎症因子 乳糖代谢 

分 类 号：R285.5[医药卫生—中药学]