百草枯中毒致大鼠肺纤维化的代谢组学研究

Metabonomic study on pulmonary fibrosis induced by paraquat poisoning in rats

目的从代谢组学的层面探索百草枯中毒致大鼠肺组织代谢损伤的作用机制,寻找用于PQ中毒的病情及预后评估的生物标志物和治疗靶点。方法将SD大鼠随机分成对照组,百草枯处理14d组和28d组,建立PQ中毒动物模型后收集三组动物的肺组织样本。WB检测肺组织纤维化标志物,采用UPLC-QTOF-MS/MS平台进行代谢组学检测,采用Metaboanalyst 4.0和SIMC-P14.1对数据进行代谢轮廓分析,筛选出差异代谢物和相关代谢通路。结果百草枯中毒大鼠肺组织出现了明显的炎症反应和肺纤维化;肺组织中差异代谢物主要涉及丙酮酸代谢、半胱氨酸和蛋氨酸代谢、氨酰基-tRNA的生物合成、组氨酸代谢、β-丙氨酸代谢通路。结论氨基酸代谢、葡萄糖代谢、脂肪代谢、能量代谢等代谢途径可能参与了PQ中毒致大鼠肺损伤的病理生理进程。

Objective To explore the mechanism of pulmonary fibrosis induced by paraquat(paraquat,PQ)poisoning in rats using metabonomics,and to find biomarkers for evaluating the condition and prognosis of PQ poisoning and therapeutic targets.Methods The SD rats were randomly divided into NC(control group),paraquat-treated 14-day group and 28-day group.The lung tissue samples of the SD rats treated with PQ were collected.The pulmonary fibrosis markers were detected by WB,the metabonomics were analyzed by UPLC-QTOF-MS/MS,and using the Metaboanalyst4.0 and SIMC-P14.1 softwares to analyze the metabolic profiles,screen out the differential metabolites and related metabolic pathways.Results The lung tissue of paraquat poisoning rats showed obvious inflammatory reaction and pulmonary fibrosis,and the differential metabolites in lung tissue were mainly involved to pyruvate metabolism,cysteine and methionine metabolism,aminoacyl-tRNA biosynthesis,histidine metabolism andβ-alanine metabolism pathway.Conclusions Amino acid metabolism,glucose metabolism,fat metabolism and energy metabolism may be involved in the pathophysiological process of pulmonary fibrosis induced by PQ poisoning in rats.