职业性矽肺患者血浆代谢组学研究

Plasma metabolomics study in patients with occupational silicosis

目的通过分析职业性矽肺患者血浆代谢组学,筛选不同期别矽肺的差异代谢通路。方法采用判断抽样方法,选择30例职业性矽肺患者为矽肺组,其中壹期、贰期、叁期亚组患者各10例;另选择10名无职业性粉尘接触史的健康对照人群为对照组。采集各组人群血浆,采用超高效液相色谱-四级杆飞行时间-质谱和非靶向代谢组学的方法对其代谢物进行鉴定。采用主成分分析法和偏最小二乘判别分析对矽肺组的代谢途径进行比较以找出差异代谢物,并采用MetaboAnanlyst 5.0等代谢分析软件探索其代谢通路。结果矽肺壹期、贰期、叁期亚组和对照组人群的血浆之间具有明显的代谢差异性;在正模式下,共筛选出149种差异代谢物,其中99种上调,50种下调。与对照组比较,矽肺壹期和贰期亚组人群的差异代谢物主要富集于鞘脂代谢、精氨酸和鸟氨酸代谢,以及脂肪酸降解等代谢通路,而矽肺叁期亚组人群的差异代谢通路富集在精氨酸和脯氨酸代谢,甘油酯类代谢,乙醛酸盐和二羧酸盐代谢,甘氨酸、丝氨酸和苏氨酸代谢通路。结论不同期别矽肺患者的血浆代谢谱均发生了明显的改变。在矽肺发病的早期和中期代谢通路以鞘脂代谢为主;在矽肺晚期以精氨酸和脯氨酸为主的代谢通路发生变化,致使肺纤维化加重。

Objective To analyze the plasma metabolomics of patients with occupational silicosis,and screen the differential metabolic pathways in different stages of silicosis.Methods Thirty patients with occupational silicosis were selected as silicosis group by judgment sampling method,including 10 patients in each subgroups with silicosis at stagesⅠ,Ⅱ,andⅢ.Another 10 healthy individuals without occupational dust exposure history were selected as the control group.Plasma of each patient was collected.The metabolites from their plasma samples were collected and identified by untargeted metabolomics using ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry.Principal component analysis and partial least square discriminant analysis were used to compare the differentially expressed metabolites.The metabolic pathways enrichment analysis was performed using MetaboAnanlyst 5.0 and other metabolic analysis software.Results There were significantly different metabolic profiles among the plasma of the silicosis subgroups and the control group.In the positive mode,149 different metabolites were screened,among which 99 metabolites were up-regulated and 50 metabolites were downregulated.Sphingolipids metabolism,arginine and ornithine metabolism,and fatty acid degradation are the main metabolic pathways in silicosis subgroups with stagesⅠandⅡcompared with the control group.The metabolic pathways of silicosis stageⅢare arginine and proline metabolism,glycerol metabolism,glyoxylic acid and dicarboxylic acid metabolism,and glycine,serine and threonine metabolism.Conclusion The plasma metabolic profile of patients with silicosis in different stages changed significantly.Sphingolipid metabolism is the main metabolic pathway in the early and middle stages of silicosis.In silicosis terminal stage,the change of arginine and proline-based metabolic pathway resulting in fibrosis aggravation.