氧化苦参碱抑制炎症因子改善高脂喂养ApoE^(-/-)小鼠胰岛素抵抗  

Oxymatrine improves fat-induced insulin resistance of ApoE^(-/-) mice by inhibiting inflammatory cytokines

作　　者：王超[1] 张会欣 邢邯英[1] 王杏[1] 张哲[1] 

机构地区：[1]河北省人民医院老年医学重点实验室,石家庄050051 [2]河北以岭医药研究院药理室,石家庄050035

出　　处：《中国新药杂志》2017年第6期670-674,共5页Chinese Journal of New Drugs

基　　金：国家重点基础研究发展计划(973计划)资助项目(2012CB518606);河北省重大医学科研资助项目(zd2013002;zd2013004)

摘　　要：目的:探讨氧化苦参碱对高脂诱导胰岛素抵抗小鼠肝脏炎症因子表达的影响,及对c-Jun氨基末端激酶(JNK)通路的作用。方法:ApoE-/-小鼠高脂喂养16周,随机数字表法分为4组,即模型组、氧化苦参碱25,50和100 mg·kg^(-1)组,C57BL/6J小鼠设为对照组,每组10只。连续灌胃(ig)给药8周。给药结束,进行小鼠葡萄糖耐量实验,并测定血糖(FBG)、甘油三酯(TG)、胆固醇(TC)、脂肪酸(FFA)和胰岛素(FINS)含量。实时荧光定量PCR(QRT-PCR)和免疫印迹分析(Western blot)检测肝组织肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素^(-1)β(IL^(-1)β)表达水平,Western blot检测肝组织JNK及磷酸化水平。结果:氧化苦参碱能不同程度降低FBG,TG,TC,FFA,改善胰岛素抵抗;与模型组比较,氧化苦参碱25 mg·kg^(-1)组IL-6表达水平降低,氧化苦参碱50和100 mg·kg^(-1)组TNF-α,IL-6,IL^(-1)β和p-JNK/JNK水平均明显降低。结论:氧化苦参碱能改善高脂诱导小鼠的胰岛素抵抗,与抑制JNK通路抑制肝脏炎症因子表达有关。Objective： To investigate the effect of oxymatrine on hepatic inflammatory cytokines in fatinduced insulin resistance（ IR） mice,and investigate the effect on c-Jun NH2-terminal kinase（ JNK） pathway.Methods： Apo E-/-mice fed with high fat diet for 16 weeks were selected as IR animal model and randomly divided into the model group,oxymatrine 25,50,100 mg·kg-1groups. C57BL/6J mice were selected as the normal control group. There were 10 mice in each group. The mice were gavage with oxymatrine for 8 weeks. Glucose tolerance test were conducted. Fasting blood glucose（ FBG）,cholesterol（ TC）,triglyceride（ TG）,fatty acid（ FFA） and serum insulin（ FINS） were detected. The expression levels of tumor necrosis factor-α（ TNF-α）,interleukin-6（ IL-6）,interleukin-1β（ IL-1β） in hepatic cells were examined by real-time PCR and western-blot.The p-JNK and JNK expression were examined by western-blot. Results： Oxymatrine reduced the levels of FBG,TG,TC,FFA and improved insulin resistance. Compared with the model group,the expression of IL-6 decreased in the oxymatrine 25 mg·kg-1group. TNF-α,IL-6,IL-1β,p-JNK/JNK expression decreased in the oxymatrine50,100 mg·kg-1group. Conclusions： Oxymatrine inhibits inflammatory cytokines in hepatic cells by inhibiting JNK pathway,thus ameliorates fat-induced insulin resistance in mice.

关 键 词：氧化苦参碱 高脂 胰岛素抵抗 炎症因子 JNK通路 

分 类 号：R587.1[医药卫生—内分泌]