目的 物质吸收入血主要基于肠-淋巴途径和门静脉途径，门静脉途径具有肝脏的生物转化作用，而肠-淋巴途径并不具备生物转化作用，其转运的物质直接进入到血液循环影响机体。本文拟探究饮酒后肠-淋巴途径所转运的物质变化及其危害性。方法 将雄性Wistar大鼠分为高、中、低剂量饮酒组和饮水组，采用灌胃的方式，分别灌胃56、28、5。6度白酒和水，10 ml·kg-1·d-1，共进行10 d，之后收集肠系膜淋巴液进行液相色谱-质谱法(liquid chromatography-mass spectrometry，LC-MS)非靶向代谢组学分析与生物信息学分析。结果 高剂量饮酒组肠系膜淋巴液中代谢物变化最大，通过对差异代谢物进行代谢组-京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析发现:高剂量饮酒组与对照组差异代谢物主要富集于癌症中的中心碳代谢、胆汁分泌、亚油酸代谢、不饱和脂肪酸的合成等通路;差异代谢物主要关联疾病有精神分裂症、阿尔茨海默病、肺癌等。中剂量与对照组的差异代谢物主要富集于苯丙氨酸代谢，缬氨酸、亮氨酸和异亮氨酸的生物合成，亚油酸代谢，胆固醇代谢等通路;差异代谢物主要关联疾病有精神分裂症、阿尔茨海默病、肺癌、帕金森病等。随着饮酒剂量的增加，淋巴液中与疾病相关的代谢物胆固醇(Cholesterol)、L-亮氨酸(L-Leucine)、富马酸(Fumaric acid)、甘露醇(Mannitol)含量增加，与精神分裂症相关的代谢物数目也有增多趋势，表明经肠-淋巴途径吸收的一些代谢物对酒精具有剂量依赖性。结论 饮酒后肠系膜淋巴液中大量代谢物发生了变化，尤其是高剂量饮酒组;饮酒可能与炎症反应、神经系统疾病、精神性疾病、癌症的发生密切相关。
Metabolomic Analysis of Mesenteric Lymph Fluid in Rats After Alcohol Gavage
Objective The absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway.The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver.On the contrary,the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly.Alcohol consumption is strongly linked to global health risk.Previous reports have analyzed the changes of metabolites in plasma,serum,urine,liver and feces after alcohol consumption.Whether alcohol consumption affects the metabolites in lymph fluid is still unknown.Therefore,it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking.Methods In this study,male Wistar rats were divided into high,medium,and low-dosage alcohol groups(receiving Chinese Baijiu at 56％,28％and 5.6％ABV,respectively)and water groups.The experiment was conducted by alcohol gavage lasting 10 d,10 ml·kg-1·d-1.Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry(LC-MS)and bioinformatic analysis.Principal component analysis and hierarchical clustering were performed by using Biodeep.Meanwhile,KEGG enrichment analysis of the differential metabolites was also performed by Biodeep.MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases.Results The metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most.Based on the KEGG enrichment analysis,the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer,bile secretion,linoleic acid metabolism,biosynthesis of unsaturated fatty acids,etc.Interestingly,in the biosynthesis of unsaturated fatty acids category,the content of arachidonic acid is increased by 7.25 times,whereas the contents of palmitic acid,oleic acid,stearic acid,arachidic acid and erucic acid all decrease,indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake.It's worth noting that arachidonic acid is closely related to inflammatory response.Furthermore,the differential metabolites are mainly related with schizophrenia,Alzheimer's disease and lung cancer.The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism,valine,leucine and isoleucine biosynthesis,linoleic acid metabolism and cholesterol metabolism.The differential metabolites are mainly related to schizophrenia,Alzheimer's disease,lung cancer and Parkinson's disease.As the dose of alcohol increases,the contents of some metabolites in lymph fluid increase,including cholesterol,L-leucine,fumaric acid and mannitol,and the number of metabolites related to schizophrenia also tends to increase,indicating that some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake.Conclusion After alcohol intake,the metabolites transported via the intestinal-lymphatic pathway are significantly changed,especially in the high-dosage group.Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake.Most importantly,alcohol intake may cause inflammatory response and the occurrence of neurological diseases,psychiatric diseases and cancer diseases.High-dosage drinking may aggravate or accelerate the occurrence of related diseases.These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.
万方数据
维普
