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代谢谱分析揭示了泼尼松治疗下MRL/lpr小鼠血清脂肪酸的异常模式。

Metabolic Profiling Reveals an Abnormal Pattern of Serum Fatty Acids in MRL/lpr Mice Under Treatment With Prednisone.

作者信息

Li Qianqian, Zhou Jia, Zhang Dingyi, Zhang Xiafeng, Xu Zhenghao, Wu Dehong

机构信息

School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Front Pharmacol. 2020 Feb 25;11:115. doi: 10.3389/fphar.2020.00115. eCollection 2020.

Abstract

Glucocorticoids (GCs) are commonly used to treat systemic lupus erythematosus (SLE). Unfortunately, excessive GCs can induce many side effects associated with disordered fatty acid (FA) metabolism. Although an increased level of total FA has been found after GCs treatment, it is not clear whether all FA species increased or only certain FA species were altered. A gas chromatography-mass spectrometry-based FA profiling approach was performed to reveal the alterations of FA species in SLE model mice (MRL/lpr) after treatment with 5 mg/kg of prednisone. The study showed a distinct FA profile in MRL/lpr mice compared to the controls, mainly manifested by elevated polyunsaturated FAs (arachidonate, docosahexaenoate, ), which are related to the inflammatory state; and altered (product FA/precursor FA) ratios representing the estimated activities of FA desaturase and elongase (higher activities of multiple elongases, △4 desaturase, △5 desaturase, △6 desaturase, and lower activity of △8 desaturase). Treatment with 5 mg/kg of prednisone decreased the total level of n-6 polyunsaturated FA in MRL/lpr mice; in particular, the level of arachidonate and estimated activity of △5 desaturase were reduced to the control level. Moreover, prednisone induced additional perturbations in FAs, including not only saturated FAs, but also monounsaturated FAs and n-3 polyunsaturated FAs, indicating that there was a strong effect of prednisone on FA metabolism. These results may be valuable for further studies of the side effects of GCs treatment.

摘要

糖皮质激素(GCs)常用于治疗系统性红斑狼疮(SLE)。不幸的是,过量的GCs会诱发许多与脂肪酸(FA)代谢紊乱相关的副作用。尽管在GCs治疗后发现总FA水平有所升高,但尚不清楚是所有FA种类都增加了,还是只有某些FA种类发生了改变。采用基于气相色谱 - 质谱的FA谱分析方法,以揭示用5mg/kg泼尼松治疗后SLE模型小鼠(MRL/lpr)中FA种类的变化。研究表明,与对照组相比,MRL/lpr小鼠具有独特的FA谱,主要表现为与炎症状态相关的多不饱和FA(花生四烯酸、二十二碳六烯酸等)升高;以及代表FA去饱和酶和延长酶估计活性的(产物FA/前体FA)比值改变(多种延长酶、Δ4去饱和酶、Δ5去饱和酶、Δ6去饱和酶活性较高,而Δ8去饱和酶活性较低)。用5mg/kg泼尼松治疗可降低MRL/lpr小鼠中n - 6多不饱和FA的总水平;特别是花生四烯酸水平和Δ5去饱和酶的估计活性降至对照水平。此外,泼尼松还会对FA产生额外的扰动,不仅包括饱和FA,还包括单不饱和FA和n - 3多不饱和FA,这表明泼尼松对FA代谢有很强的影响。这些结果可能对进一步研究GCs治疗的副作用具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e53/7052041/45d7710e5ee6/fphar-11-00115-g001.jpg

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