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胶原诱导性关节炎(CIA)大鼠关节组织的代谢指纹图谱:基于体外高分辨率核磁共振(NMR)光谱的分析。

Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro, high resolution NMR (nuclear magnetic resonance) spectroscopy based analysis.

作者信息

Srivastava Niraj Kumar, Sharma Shikha, Sharma Rajkumar, Sinha Neeraj, Mandal Sudhir Kumar, Sharma Deepak

机构信息

Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067.

Center of Biomedical Research, Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Lucknow-226014, India.

出版信息

EXCLI J. 2018 Mar 19;17:257-272. doi: 10.17179/excli2017-938. eCollection 2018.

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA.

摘要

类风湿性关节炎(RA)是一种全身性自身免疫性疾病,其主要特征是持续性关节炎症,可导致关节破坏和功能丧失。胶原诱导性关节炎(CIA)大鼠是一种自身免疫性疾病模型,在许多方面与RA具有相似特征。CIA与全身表现有关,包括代谢改变。基于核磁共振(NMR)光谱的代谢组学已成功应用于CIA大鼠和对照大鼠关节组织的高氯酸提取物,用于分析水溶性代谢物。与对照大鼠相比,甘油磷酸胆碱(GPC)、肉碱、乙酸盐和肌酐是CIA大鼠的重要判别指标。与对照大鼠相比,CIA大鼠的乳酸水平(显著性;p = 0.004)、丙氨酸水平(p = 0.025)、支链氨基酸(BCA)水平(p = 0.006)和肌酐水平(p = 0.023)显著更高。与对照大鼠相比,CIA大鼠的胆碱(p = 0.038)和GPC(p = 0.009)显著降低。CIA大鼠以及对照大鼠的胆碱与GPC相关性良好且呈负相关(Pearson相关性 = -0.63,对照大鼠Pearson相关性 = -0.79)。与对照大鼠相比,所有这些分析共同被视为CIA大鼠关节组织的代谢指纹图谱。CIA大鼠关节组织的代谢指纹图谱与对照大鼠不同。代谢指纹图谱反映了CIA大鼠伴有滑膜炎时的炎症疾病活动,表明潜在的炎症过程驱动了可在关节组织中测量的显著代谢变化。因此,本研究结果可能有助于理解RA中代谢过程的机制。这也可能有助于开发RA的先进诊断方法和治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b5/5938536/998bb37821b9/EXCLI-17-257-g-001.jpg

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