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氧化苦参碱对高脂诱导胰岛素抵抗ApoE-/-小鼠肝脏成纤维细胞因子-21/β-klotho/FGF-21受体1通路的作用

Effect of oxymatrine on hepatic FGF-21/β-klotho/FGFRl pathway in ApoE-/- mice with fat-induced insulin resistance

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【作者】 王超张会欣邢邯英王杏张哲

【Author】 WANG Chao;ZHANG Hui-xin;XING Han-ying;Key Laboratory of Geriatrics Hebei General Hospital;

【机构】 河北省人民医院老年医学重点实验室河北以岭医药研究院药理室

【摘要】 目的探讨氧化苦参碱(OXY)对高脂诱导IR ApoE-/-小鼠肝脏成纤维细胞因子-21(FGF-21)/β-klotho/FGF-21受体1(FGFR1)通路的作用。方法 ApoE-/-小鼠分为模型(IR)组、氧化苦参碱25 mg/kg(IR+25OXY)组、氧化苦参碱50 mg/kg(IR+50OXY)组、氧化苦参碱100 mg/kg(IR+100OXY)组,C57BL/6J小鼠作为对照(NC)组。计算HOMA-IR和ISI。QRT-PCR和Western blot检测肝组织FGF-21、β-klotho蛋白(β-klotho)、FGFR1表达。结果与IR组比较,IR+50OXY组和IR+100OXY组HOMA-IR值降低[(31.54±4.30)vs(21.84±1.87)vs(17.27±3.59)],ISI值升高[(0.022±0.000)vs(0.034±0.010)vs(0.042±0.010)](P<0.05);OXY可使FGF-21、β-klotho、FGFR1 mRNA和蛋白表达有不同程度的降低。结论 OXY能通过调节肝脏FGF-21/β-klotho/FGFR1通路,改善高脂诱导小鼠的IR。

【Abstract】 Objective To investigate the effect of oxymatrine(OXY) on hepatic FGF-21 /β-klotho/FGFR1 pathway in ApoE-/- mice with fat-induced insulin resistance.Methods ApoE-/- mice were divided into model group(IR),oxymatrine 25 mg/kg group(IR + 25OXY),oxymatrine 50 mg/kg group(IR+50OXY),and oxymatrine 100 mg/kg group(IR+ 100OXY).C57BL/6J mice were selected as normal control group(NC).Insulin resistance index(HOMA-IR) and insulin sensitivity index(ISI) were calculated.The expression of fibroblast growth factor 21(FGF-21),β-klotho protein family(β-klotho) and FGF-21 receptor 1(FGFR1) were examined by QRT-PCR and Western-blot.Results HOMA-IR decreased in IR+50 OXY group and IR+100 OXY group than in IR group[(21.84 ± 1.87) vs(17.27 ±3.59) vs(31.54 ± 4.30),P<0.05].ISI increased in IR+50 OXY group and IR+100 OXY group than in IR group[(0.034 ± 0.010) vs(0.042 ± 0.010) vs(0.022 ± 0.000),P<0.05].Oxymatrine reduced the mRNA and protein expression of FGF-21,β-klotho and FGFR1 in different degree.Conclusion Oxymatrine can improve fat-induced insulin resistance in mice by modulating the hepatic FGF-21/β-klotho/FGFR1 pathway.

【基金】 国家重点基础研究发展计划(973计划)项目(2012CB518606);河北省重大医学科研项目(zd2013002、zd2013004)
  • 【文献出处】 中国糖尿病杂志 ,Chinese Journal of Diabetes , 编辑部邮箱 ,2016年11期
  • 【分类号】R285.5
  • 【被引频次】7
  • 【下载频次】195
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