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采用超高效液相色谱-轨道阱质谱联用技术对肾精亏虚痴呆大鼠尿液代谢轮廓的研究

Urine metabolic profiling of dementia rats with vital energy deficiency using ultra-high-performance liquid chromatography coupled with an orbitrap mass spectrometer.

机构信息

College of Chemistry, Jilin University, Changchun, P. R. China.

National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, P. R. China.

出版信息

J Sep Sci. 2022 Jan;45(2):507-517. doi: 10.1002/jssc.202100837. Epub 2021 Nov 25.

DOI:10.1002/jssc.202100837
PMID:34779121
Abstract

Dementia is a chronic and multifactor-induced neurodegenerative disorder that occurs frequently in the elderly with weak constitution and insufficient vital energy. However, the relationship between vital energy deficiency and the occurrence and development of dementia is still unclear. In this study, a rat model of dementia with vital energy deficiency was established through intraperitoneal injection with d-galactose and AlCl and combined with exhaustive swimming. Changes in the dementia with vital energy deficiency rat model were assessed by examining behaviors, hippocampal histopathological and biochemical parameters, and serum biochemical parameters. Urine metabolomics based on ultra-high-performance liquid chromatography coupled with an orbitrap mass spectrometer was also used to discover endogenous metabolic profile and disease-related biomarkers and investigate the potential mechanism of dementia with vital energy deficiency. Among the 31 potential biomarkers that were identified, nine involved metabolic pathways. The four main types were phenylalanine, tyrosine and tryptophan metabolism, taurine and hypotaurine metabolism, and citrate cycle and pyrimidine metabolism. The pathogenesis of dementia with vital energy deficiency is mainly neurotoxin accumulation and body aging that leads to oxidative stress injury and loss of neuronal protective substances. Vital energy deficiency inhibits the body's energy metabolism and eventually leads to aggravate the dementia.

摘要

痴呆症是一种慢性、多因素诱导的神经退行性疾病,常见于体质虚弱、元气不足的老年人。然而,元气不足与痴呆症的发生发展之间的关系尚不清楚。本研究通过腹腔注射半乳糖和 AlCl 联合力竭游泳,建立了元气不足型痴呆大鼠模型。通过检测行为、海马组织病理和生化参数以及血清生化参数来评估元气不足型痴呆大鼠模型的变化。还基于超高效液相色谱-轨道阱质谱联用技术进行了尿液代谢组学研究,以发现内源性代谢谱和与疾病相关的生物标志物,并探讨元气不足型痴呆的潜在机制。在鉴定的 31 个潜在生物标志物中,有 9 个涉及代谢途径。四种主要类型是苯丙氨酸、酪氨酸和色氨酸代谢、牛磺酸和次牛磺酸代谢以及柠檬酸循环和嘧啶代谢。元气不足型痴呆的发病机制主要是神经毒素积累和机体衰老导致氧化应激损伤和神经元保护物质的丧失。元气不足抑制了机体的能量代谢,最终导致痴呆症加重。

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