基于血浆非靶向代谢组学的慢性疲劳综合征大鼠发病机制的初步研究  

Mechanism of chronic fatigue syndrome in rats based on plasma non-targeted metabolomics

作　　者：苏芮 王婷婷 田骄 裴海鸾 许明阳 左泽平 王晶[1] SU Rui;WANG Ting-ting;TIAN Jiao;PEI Hai-luan;XU Ming-yang;ZUO Ze-ping;WANG Jing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488;Pharmaceutical Factory,Beijing Tongrentang Technologies Co.,Ltd.,Beijing 100071;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京同仁堂科技发展股份有限公司制药厂,北京100071 [3]北京中医药大学中医学院,北京102488

出　　处：《中南药学》2025年第1期32-40,共9页Central South Pharmacy

基　　金：国家重点研发计划(No.2019YFC1711400)。

摘　　要：目的基于血浆非靶向代谢组学及相关指标的测定,初步探究多因素复合应激诱导的慢性疲劳综合征(CFS)大鼠的发病机制。方法采用多因素复合应激诱导的CFS大鼠模型,造模6周后,进行力竭游泳、悬尾、高架十字迷宫、戊巴比妥钠诱导睡眠、机械性缩足反射阈值(MWT)及巴恩斯迷宫行为学实验;采用高效液相色谱-质谱联用技术进行血浆非靶向代谢组学检测;生化法检测骨骼肌丙酮酸、三磷酸腺苷(ATP)、丙二醛(MDA)及还原型谷胱甘肽(GSH)含量,以及丙酮酸脱氢酶(PDH)、琥珀酸脱氢酶(SDH)、ATP合酶、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性。结果与空白组相比,模型组大鼠下沉潜伏期、睡眠持续时间显著缩短,开放臂滞留时间百分比(OT%)、痛阈阈值显著降低(P<0.01);悬尾累计不动时间、巴恩斯迷宫实验探索洞口潜伏期显著延长(P<0.01);模型组共有851种代谢产物发生变化,发现了乙醛酸和二羧酸代谢、嘌呤代谢等与CFS有显著相关性的通路;骨骼肌丙酮酸、ATP及GSH含量显著降低(P<0.05或0.01);MDA含量显著升高(P<0.01);PDH、SDH、ATP合酶、SOD及GSH-Px活性显著降低(P<0.01)。结论三羧酸循环障碍及线粒体功能障碍引起的机体能量代谢紊乱可能是CFS的发病机制之一。Objective To preliminarily explore the pathogenesis of rats with chronic fatigue syndrome(CFS)induced by multifactor compound stress based on non-targeted plasma metabolomics and determination of related indicators.Methods The rat model of CFS was adopted.After 6 weeks of modeling,we conducted behavioral experiments including exhaustive swimming experiment,tail suspension experiment,elevated cross maze experiment,pentobarbital sodium induced sleep experiment,mechanical pain threshold experiment,and Barnes maze experiment.LC-MS method was used to detect non-targeted metabolomics in the plasma.The contents of pyruvate,adenosine tri-phosphate(ATP),malondialdehyde(MDA)and reduced glutathione(GSH),and the activities of pyruvate dehydrogenase(PDH),succinate dehydrogenase(SDH),ATP synthase,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the skeletal muscle were detected by biochemical methods.Results Compared with the blank group,the subsidence latency,sleep duration,the percentage of open arm lag time,and pain threshold of rats in the model group were significantly decreased(P<0.01).The accumulative immobile time in the tail hanging experiment and the incubation period in the Barnes maze experiment were significantly increased(P<0.01).Totally 851 metabolites in the model group showed certain change.The pathways of glyoxylate and dicarboxylate metabolism and purine metabolism were found to be significantly related to CFS.The contents of pyruvate,ATP and GSH in the skeletal muscle were significantly decreased(P<0.05 or 0.01).MDA content was significantly increased(P<0.01),while the activities of PDH,SDH,ATP synthase,SOD and GSH-Px were significantly decreased(P<0.01).Conclusion The disturbance of energy metabolism caused by tricarboxylic acid cycle circulation disorder and mitochondrial dysfunction may be a possible pathogenesis of CFS.

关 键 词：慢性疲劳综合征 多因素复合应激 非靶向代谢组学 能量代谢 

分 类 号：R96[医药卫生—药理学]