代谢组学法考察金银花醇提物对模型小鼠肝损伤的预防作用

Observation of Preventive Effect of Lonicera japonica Alcohol Extract on Mice with Liver Injury by Metabolomics Method

目的：基于代谢组学法研究金银花醇提物对模型小鼠肝损伤的预防作用。方法：30只小鼠随机均分为正常对照（等容生理盐水）组、模型（等容生理盐水）组与金银花醇提物（2 g/kg）组,ig给药,每天1次,连续14 d;给药第8天开始复制模型[ip给予0.2%二甲基亚硝胺（DMN,10 ml/kg）,每天1次,连续7 d]。通过气相色谱与质谱联用（GC-MS）分析开始给药与开始给予DMN第1、3、5、7天小鼠24 h尿样总离子流图,考察尿样中内源性小分子代谢物的变化,主成分分析法探寻尿样代谢物谱的变化及潜在的生物标记物。结果：金银花醇提物组小鼠给予DMN 1~5 d后,色谱图轮廓发生变化并达到最大,但第7天呈明显回归趋势;DMN可导致小鼠尿样内源性小分子代谢物中8-苯基-8-氮杂环[4,3,0]壬-3-烯-7,9-二酮、2-（6-苯基庚炔）-1,3-二氧戊烷、双-（邻-甲基肟）-4-酮葡糖酸含量增加,丙二酸、（4-氯苯基硫代甲氧基）乙酸、四氢-2-呋喃乙醛、D-半乳糖、赤式戊糖酸、半乳糖醛酸含量减少;金银花醇提物能改善这一情况。结论：预先ig给予金银花醇提物对DMN诱导的小鼠肝损伤有一定预防作用。

OBJECTIVE：To study the preventive effect of Lonicera japonica alcohol extract on mice with liver injury based on metabolomics method.METHODS：30 mice were equally randomized into a normal control（isometric normal saline） group,a model（isometric normal saline）group and a group of L.japonica alcohol extract（2 g/kg）.The mice were given drugs by ig once a day for 14 consecutive days.On the 8th day of administration,the models were established by giving 0.2% dimethyl sulfoxide（DMN,10 ml/kg）ip once a day for 7 consecutive days.Gas chromatography-mass spectrum（GC-MS）was used to analyze 24 h total ions chromatogram of the urine sample on the 1st,3rd,5th and 7th day of administration of drugs and DMN.The change in endogenic small molecule metabolites in urine was observed.Principal component analysis was employed to explore the change in the metabolite chromatogram and underlying biomarkers in urine.RESULTS：The contour of the chromatogram changed to a largest extent 1 to 5 d after given DMN,but showed an obvious trend towards regression 7 days thereafter.DMN resulted in increase in the contents of 8-phenyl-8-azbicyclo-[4,3,0]non-3-ene-7,9-dione,2-（6-heptynyl）-1,3 dioxolane,bis-（O-methyloxime）-4-ketoglucose,and decrease in the contents of malonic acid,2-（4-chlorophenylthiomethoxyl）ethyl,tetrahydro-2-furanacetaldehyde,D-galactose,erythro-pentonic acid and galacturonic acid,in endogenic small molecule metabolites in mouse urine,for which Lonicera japonica alcohol extract can improve that.CONCLUSIONS：Previous administration of L.japonica alcohol extract ig has preventive effect to some extent on the physiological and metabolic conditions of mice with liver injury induced by DMN.