基于代谢组学研究1-甲基海因对百草枯中毒防护机制

目的基于气相色谱-质谱联用技术(GC-MS)分析1-甲基海(MH)因防护百草枯(PQ)中毒模型,研究其代谢组学特征及其密切相关的代谢产物,探讨其分子机制及特征代谢物的潜在临床价值。方法PQ组为灌胃30mg/kg百草枯建立昆明小鼠中毒模型,PQ+MH组为灌胃30mg/kg百草枯后腹腔注射100mg/kg的MH生理盐水溶液,NS组为灌胃30mg/kg后腹腔注射100mg/kg生理盐水的对照组。实验结束时取脏器和血液,染色、分析,应用GC-MS技术分别对三组小鼠血清样本进行检测,多变量统计学分析,筛选出具有显著意义的差异代谢物。结果1-甲基海因干预后,百草枯中毒小鼠肾组织的炎症情况改善,SOD活性显著升高,MDA含量显著降低,血清中代谢产物硬脂酸、软脂酸、丝氨酸、酪氨酸、蛋氨酸、2-羟基丁酸,草酸,3-羟基丙酸、牛磺酸、6-磷酸葡糖酸、阿拉伯糖醇、甘油酸的含量增加。结论1-甲基海(MH)具有抗氧化性和减轻百草枯致肾损伤的作用,与对氨基酸代谢、糖代谢、脂肪酸代谢的调节相关。

The protective mechanism of 1-methylhydantoin on the paraqaut toxicity basing on the metabolomics

Objective To analyze the protective mechanism of 1-methylhydantoin on paraquat poisoning using GC-MS basing on metabolomics.Methods Fifteen SPF healthy Kunming mice were randomly divided into normal saline(NS)control group,PQ poisoning model group and MH intervention group,with 5 mice in each group.Paraquat poisoning mice model was established by gavage of 30 mg/kg paraquat solution.The NS group received the same amount of NS by gavage.The MH group were given 100 mg/kg of MH immediately after the model was made.Mice were sacrificed 1 day after gavage and heart blood and renal tissue were harvested for examination.The morphological changes of renal tissue were observed under light microscope by HE staining.The content of MDA and the activity of SOD in lung tissue were detected according to the instruction of the kit.Moreover,the serum samples of the PQ poisoning group and the MH+PQ group were detected by GC-MS.Multivariate statistical analysis was performed to screen out the metabolites with significant difference.Results After the intervention of 1-methylhydantoin,the degree of kidney tissues was significantly improved in rats of PQ+MH group;SOD activity was significantly increased;MDA content was significantly decreased;MH+PQ group’s palmitic acid,stearic acid,serine,tyrosine,methionine,2-hydroxy butyric acid,oxalic acid,3-hydroxypropionic acid,taurine,oxalic acid,D-glyceric acid and 6-phosphogluconic acid were increased.Conclusion The antioxidant effect and reducing paraquat induced kidney injury of 1-methylhydantoin is related to the regulation on metabolomics.