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MPTP/丙磺舒诱导的帕金森病小鼠模型中的代谢紊乱:使用液相色谱-质谱联用技术进行评估

Metabolic Disturbances in a Mouse Model of MPTP/Probenecid-Induced Parkinson's Disease: Evaluation Using Liquid Chromatography-Mass Spectrometry.

作者信息

Wang Yueyuan, Lv Bo, Fan Kai, Su Cunjin, Xu Delai, Pan Jie

机构信息

Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.

出版信息

Neuropsychiatr Dis Treat. 2024 Aug 27;20:1629-1639. doi: 10.2147/NDT.S471744. eCollection 2024.

Abstract

PURPOSE

Parkinson's disease (PD) is a common neurodegenerative disease that severely affects patients' daily lives and places a significant burden on the global economy. There are currently no specific biomarkers for distinguishing between the different stages of PD.

METHODS

We divided 78 mice into six equal groups, including five model PD groups (W1-W5; based on the PD stage induced by length of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/propofol induction time) and a control group. Then, we used metabolomics technology to detect the serum small-molecule metabolites present in each group. Ultimately, we screened for potential biomarkers using the variable importance in the projection of the orthogonal partial least squares discriminant analysis and the coefficient value of LASSO ordinal logistic regression.

RESULTS

We identified 12 potential biomarkers, including dehydroepiandrosterone sulfate, pipecolic acid, N-acetylleucine, 2-aminoadipic acid, L-tyrosine, uric acid, and 5-hydroxyindoleacetaldehyde. Pathway analysis revealed their involvement in amino acid metabolism, caffeine metabolism, steroid hormone biosynthesis, and purine metabolism. Additionally, the receiver operating characteristic curve indicated that a biomarker panel comprising the 12 biomarkers could differentiate between the different PD stages.

CONCLUSION

Different PD stages are characterized by different metabolites. The biomarkers identified in this study are helpful to understand the PD process.

摘要

目的

帕金森病(PD)是一种常见的神经退行性疾病,严重影响患者的日常生活,并给全球经济带来巨大负担。目前尚无用于区分PD不同阶段的特异性生物标志物。

方法

我们将78只小鼠分为六个相等的组,包括五个PD模型组(W1-W5;基于1-甲基-4-苯基-1,2,3,6-四氢吡啶/丙泊酚诱导时间的长短所诱导的PD阶段)和一个对照组。然后,我们使用代谢组学技术检测每组中存在的血清小分子代谢物。最终,我们使用正交偏最小二乘判别分析的投影变量重要性和LASSO有序逻辑回归的系数值筛选潜在的生物标志物。

结果

我们鉴定出12种潜在的生物标志物,包括硫酸脱氢表雄酮、哌啶酸、N-乙酰亮氨酸、2-氨基己二酸、L-酪氨酸、尿酸和5-羟吲哚乙醛。通路分析表明它们参与氨基酸代谢、咖啡因代谢、类固醇激素生物合成和嘌呤代谢。此外,受试者工作特征曲线表明,由这12种生物标志物组成的生物标志物组可以区分不同的PD阶段。

结论

不同的PD阶段具有不同的代谢物特征。本研究中鉴定出的生物标志物有助于理解PD的发病过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56cd/11365497/3a3ca23d3c7b/NDT-20-1629-g0001.jpg

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