纤维细胞生长因子-21抑制脂多糖诱导的急性炎症及其分子机制研究

李思明,王文飞,曹宏雪,杨永碧,李德山

中国药学杂志 ›› 2016, Vol. 51 ›› Issue (15) : 1282-1288.

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中国药学杂志
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中国药学杂志 ›› 2016, Vol. 51 ›› Issue (15) : 1282-1288. DOI: 10.11669/cpj.2016.15.006
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纤维细胞生长因子-21抑制脂多糖诱导的急性炎症及其分子机制研究

  • 李思明1,王文飞2,曹宏雪2,杨永碧2,李德山2
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FGF-21 Inhibits Lipopolysaccharide Induced Acute Inflammation and Its Molecular Mechanism

  • LI Si-ming1,WANG Wen-fei2 , CAO Hong-xue2 ,YANG Yong-bi2,LI De-shan2
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摘要

目的 研究成纤维细胞生长因子-21(fibroblast growth factor-21,FGF-21)抑制脂多糖(LPS)诱导的急性炎症的作用及机制。 方法 构建LPS诱导的小鼠急性炎症模型,FGF-21高、中、低剂量进行处理后,HE染色法观察肺部组织病理学变化,ELISA法检测血清中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、IL-17含量,实时荧光定量聚合酶链反应(PCR)法检测TNF-α、IL-1β、IL-6、IL-17表达量,激光共聚焦和Western blot法检测腹腔巨噬细胞核因子(NF)-κB蛋白向细胞核内转移情况。结果 FGF-21干预后,模型小鼠肺部损伤明显减轻,炎性浸润细胞减少。血清和腹腔巨噬细胞中TNF-α、IL-1β、IL-6、IL-17含量均显著降低且成剂量依赖性趋势。激光共聚焦和Western-blot结果均显示,FGF-21能够抑制NF-κB向细胞核内转移。结论 FGF-21能够作用于巨噬细胞调控机体免疫系统,通过NF-κB信号通路缓解小鼠炎症反应状态可能是FGF-21调节免疫系统的机制之一。

Abstract

OBJECTIVE To study the effects of fibroblast growth factor-21(FGF-21) on acute inflammation induced by lipopolysaccharide (LPS)and its mechanism. METHODS Mouse model of acute inflammation was established by injection of LPS and treated with FGF-21 at high, medium and low doses, the pathological changes were detected with HE staining, the expression level of TNF-α, IL-1β, IL-6 and IL-17 in serum and peritoneal macrophage were determined by ELISA and Real-time PCR. NF-κB p65 in macrophage cells was analyzed by confocal laser scanning microscope and Western-blotting. RESULTS FGF-21 treatment reduced lung damage and inflammatory cell infiltration and decreased the expression level of TNF-α, IL-1β, IL-6 and IL-17 in both serum and peritoneal macrophage. The results of confocal laser scanning microscope and Western-blotting both showed that FGF-21 could inhibit NF-κB transferring to the nucleus. CONCLUSION FGF-21 could regulate the immune system by acting on macrophage. Relieving the inflammatory response in mice through NF-κB signal pathway may be one of the mechanisms FGF-21 regulating immune system.

关键词

成纤维细胞生长因子-21 / 脂多糖 / 急性炎症 / 免疫系统 / 核因子-κB信号通路

Key words

fibroblast growth factor-21 / lipopolysaccharide / acute inflammation / immune system / NF-κB signal pathway

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李思明,王文飞,曹宏雪,杨永碧,李德山. 纤维细胞生长因子-21抑制脂多糖诱导的急性炎症及其分子机制研究[J]. 中国药学杂志, 2016, 51(15): 1282-1288 https://doi.org/10.11669/cpj.2016.15.006
LI Si-ming,WANG Wen-fei , CAO Hong-xue ,YANG Yong-bi,LI De-shan. FGF-21 Inhibits Lipopolysaccharide Induced Acute Inflammation and Its Molecular Mechanism[J]. Chinese Pharmaceutical Journal, 2016, 51(15): 1282-1288 https://doi.org/10.11669/cpj.2016.15.006
中图分类号： R965   

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基金

黑龙江省应用技术研究与开发计划资助项目(GC14D205);哈尔滨商业大学博士科研启动项目(92508177)
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