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脂质组学分析加深对尿酸钠结晶注射联合高脂饮食诱导的痛风模型分子机制及别嘌醇干预机制的理解。

Lipidomics Analysis Deepen Understanding the Molecular Mechanisms in a Gouty Model Induced by Combination of MSU Crystals Injection and High-Fat Diet Feeding and the Intervention Mechanisms of Allopurinol.

作者信息

Li Dianming, Shi Weiman, Hu Changfeng, Wen Chengping, Huang Lin, Wang Qiao

机构信息

College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou City, People's Republic of China.

Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Hangzhou City, People's Republic of China.

出版信息

J Inflamm Res. 2024 Feb 13;17:1003-1018. doi: 10.2147/JIR.S443358. eCollection 2024.

Abstract

BACKGROUND

Gouty arthritis (GA) is a common inflammatory disease caused by deposition of monosodium urate (MSU) crystals in diarthrodial joints. GA attacks commonly involved in joint with red, swollen, heat and pain, and often happened in unilateral foot-first metatarsophalangeal. Accumulated studies have proved that lipids play critical roles in biological processes and lipids biomarkers can substitute for the diagnosis of various diseases.

METHODS

Herein, shotgun lipidomics was used to quantitatively analyze serum lipidomes of a gouty model which was induced by injecting MSU crystals and feeding high-fat diet with/without treatment with allopurinol. Meanwhile, ELISA kit was used to detect mouse serum levels of inflammatory cytokines (eg, tumor necrosis factor-α, interleukin 1 beta) and HE staining was used to observe the infiltration of inflammatory cells in the foot pad.

RESULTS

A total of 9 types of serum lipids were detected in lipidomics by shotguns, and the result of NMDS' analysis demonstrated significant differences in lipids profiles between the control and model group. It is worth noting that lipid abnormality in GA (such as Ceramide (Cer), sphingomyelin (SM), 4-hydroxyalkenals (HNE), phosphatidylinositol (PI), ethanolamine glycerophospholipid (PE), etc.) is related with phospholipid and energy metabolism, and allopurinol treatment could correct the aberrant metabolism of lipid to some extent.

CONCLUSION

Our results indicated that various aberrant lipid metabolisms were present in the established gouty model, and allopurinol treatment could relief this aberrant metabolism of lipids to some degree.

摘要

背景

痛风性关节炎(GA)是一种常见的炎症性疾病,由尿酸单钠(MSU)晶体在滑膜关节中沉积引起。GA发作通常累及关节,表现为红、肿、热、痛,且常发生于单侧足部第一跖趾关节。越来越多的研究证明,脂质在生物过程中起关键作用,脂质生物标志物可用于多种疾病的诊断。

方法

在此,采用鸟枪法脂质组学对注射MSU晶体并给予高脂饮食诱导的痛风模型血清脂质组进行定量分析,该模型接受或不接受别嘌醇治疗。同时,使用酶联免疫吸附测定试剂盒检测小鼠血清中炎症细胞因子(如肿瘤坏死因子-α、白细胞介素1β)水平,并采用苏木精-伊红染色观察足垫中炎症细胞浸润情况。

结果

通过鸟枪法脂质组学共检测到9种血清脂质,非度量多维尺度分析结果表明,对照组和模型组脂质谱存在显著差异。值得注意的是,GA中的脂质异常(如神经酰胺(Cer)、鞘磷脂(SM)、4-羟基烯醛(HNE)、磷脂酰肌醇(PI)、乙醇胺甘油磷脂(PE)等)与磷脂和能量代谢有关,别嘌醇治疗可在一定程度上纠正脂质代谢异常。

结论

我们的结果表明,在建立的痛风模型中存在多种脂质代谢异常,别嘌醇治疗可在一定程度上缓解这种脂质代谢异常。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac3e/10874778/9e0d1e12a981/JIR-17-1003-g0001.jpg

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