基于脂质组学分析揭示高原低氧对小鼠脾组织磷脂代谢的调控机制

Lipidomic Analysis Revealed the Regulatory Mechanism of High Altitude Hypoxia on Phospholipid Metabolism in Mouse Spleen Tissue

脾是机体最大的淋巴器官,参与病原体清除和抗体产生的免疫反应过程,并参与代谢平衡调节。高原低氧环境可影响脾组织脂质代谢,但影响脂质代谢的关键机制仍不清楚。我们旨在使用脂质组学分析方法研究高原低氧对小鼠脾组织脂质代谢的影响。将C57BL/6小鼠分别置于海拔4200 m(高原低氧组,HST组)和400 m(平原常氧组,PSC组),30 d取脾组织。使用超高效液相色谱-Orbitrap质谱系统进行脂质组学分析。30 d时在高原低氧环境下,小鼠脾指数降低,并出现白髓减少,生发中心扩大,边缘模糊,静脉充血等病理学改变。脂质组学分析结果显示,共鉴定到41种脂质亚类和2473种脂质分子,甘油三酯(triacylglycerides,TGs)和磷脂酰胆碱(phosphatidylcholines,PCs)为脂质分子鉴别到最多的2种。使用单变量和多变量分析,鉴定到44个差异脂质分子,它们主要集中于磷脂代谢。随后,对磷脂代谢途径中的关键酶进行RT-qPCR检测,发现其mRNA表达量均有差异(P<0.05)。提示高原低氧环境主要影响小鼠脾组织磷脂代谢,并通过减少PC和磷脂酸(phosphatidic acid,PA)含量,促进其转化为磷脂酰乙醇胺(phosphatidylethanolamine,PE)和心磷脂(cardiolipin,CL)并通过CDP-乙醇胺(CDP-Ethanolamine,CDP-Etn)途径促进PE生成。该研究为高原低氧环境下脾组织中磷脂代谢异常提供新的实验依据。

The spleen is the largest lymphoid organ of the body,which participates in the regulation of metabolic balance.High altitude hypoxia environment can affect lipid metabolism in spleen tissue,but the key mechanism of lipid metabolism is still unclear.We aimed to use lipidomic analysis to study the effect of high altitude hypoxia on lipid metabolism in mouse spleen tissue.C57BL/6 mice were placed at an altitude of 4200 m and 400 m,respectively,and after 30 days the spleen tissues were harvested and lipidomic analysis was performed using an ultra-high performance liquid chromatography-Orbitrap mass spectrometry system.Under the high altitude hypoxia environment,the spleen index of mice and the white pulp decreased,and the germinal center expanded with other pathological changes.The results of lipidomic analysis showed that a total of 41 lipid subclasses and 2473 lipid molecules were identified,and triacylglycerides(TGs)and phosphatidylcholines(PCs)were the two most identified lipid molecules.Using univariate and multivariate analysis,44 differentially expressed lipid molecules were identified,which were mainly concentrated in phospholipid metabolism.Subsequently,RT-qPCR was performed on the key enzymes in the phospholipid metabolic pathway,and it was found that the mRNA expression levels were different(P<0.05).It suggested that high altitude hypoxia environment mainly affects the phospholipid metabolism of mouse spleen tissue via reducing the contents of PC and phosphatidic acid(PA),promoting their conversion to phosphatidylethanolamine(PE)and cardiolipin(CL)and facilitating the PE production via the CDP-Etn pathway.This study provides a new experimental basis for the abnormal metabolism of phospholipids in spleen tissue under high altitude hypoxia environment.