老龄自发性高血压大鼠和Wistar-Kyoto大鼠血浆代谢组学的比较研究

Comparative Study on Plasma Metabolomics of Aged SHR and WKY Rats

目的探寻老龄自发性高血压大鼠(SHR)的特征性生物代谢标志物及代谢通路。方法选择清洁级SHR12只,雌雄各半,58周龄,作为模型组(A),同时将Wistar-Kyoto大鼠WKY12只,雌雄各半,58周龄,作为对照组(B);一方面记录两组大鼠的收缩压及舒张压水平;另一方面采用超高效液相色谱-四级杆-静电场轨道阱高分辨质谱联用技术(UPLC-Q-Exactive)对比分析老龄SHR和WKY大鼠体内血浆代谢物的差异,筛选并确定老龄SHR的特征性生物代谢标志物及相关的代谢通路。结果筛选出老龄SHR的特征性生物代谢标记物共有20个;同时鉴定出与老龄SHR密切相关的6条代谢通路,包括亚油酸代谢、苯丙氨酸代谢、甘油磷脂代谢、精氨酸和脯氨酸代谢、甾体类激素生物合成及苯丙氨酸、酪氨酸和色氨酸生物合成等。结论老龄自发性高血压大鼠体内可能存在着亚油酸代谢、苯丙氨酸代谢、甘油磷脂代谢、精氨酸和脯氨酸代谢、甾体类激素生物合成及苯丙氨酸、酪氨酸和色氨酸生物合成的紊乱;初步从代谢组学的层面解读了老年高血压病可能的发病机制,为研究疾病发生发展的病理生理过程及寻找疾病新的生物标志物开拓了崭新的思路。

Objective To explore the characteristic biological metabolic markers and metabolic pathways of aged spontaneous hypertension rats(SHR).Methods We selected 12 clean grade SHR,half male and half female,58 weeks old,as the model group(A).At the same time,12 Wistar-Kyoto(WKY)rats,half male and half female,58 weeks old,were used as the control group(B).On the one hand,the systolic and diastolic blood pressure levels of the two groups were recorded.On the other hand,UPLC-Q-Exactive was used to compare and analyze the differences of plasma metabolites in aged SHR and WKY rats,so as to screen and determine the specific biological metabolic markers and related metabolic pathways of the aged SHR.Results A total of 20 biological metabolic markers with special characteristics of the aged SHR were screened.Meanwhile,six metabolic pathways closely related to the aged SHR were identified,including linoleic acid metabolism,phenylalanine metabolism,glycerolipid metabolism,arginine and proline metabolism,steroidal hormone biosynthesis and phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion There may be disorders of linoleic acid metabolism,phenylalanine metabolism,glycerolipid metabolism,arginine and proline metabolism,steroidal hormone biosynthesis and phenylalanine,tyrosine and tryptophan biosynthesis in aged SHR.The possible pathogenesis of hypertension in the elderly was preliminarily interpreted from metabolomics.It opens up a new way to study the pathophysiological process of disease occurrence and development and search for new biomarkers of disease.