氧化苦参碱抑制p38MAPK通路减轻高脂喂养胰岛素抵抗小鼠氧化应激

Oxymatrine alleviates oxidative stress in fat-induced insulin resistance mice by suppressing p38MAPK pathway

该研究通过观察氧化苦参碱对高脂诱导胰岛素抵抗(IR)小鼠的影响,试探讨其对IR小鼠肝脏氧化应激及对p38丝裂原活化蛋白激酶(p38MAPK)通路的作用。实验以高脂喂养Apo E-/-小鼠16周为IR模型,随机数字表法分为4组,即胰岛素抵抗组,氧化苦参碱低、中、高剂量(25,50,100 mg·kg^(-1))组,C57BL/6J小鼠设为对照组,灌胃给药8周。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;测定肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量;流式细胞术检测肝细胞活性氧簇(ROS)含量;荧光定量PCR和Western blot测定肝组织血红素氧合酶-1(HO-1)、γ-谷氨酰半胱氨酸合成酶(γ-GCS)表达;Western blot测定肝组织p38MAPK,p-p38MAPK蛋白表达。研究发现氧化苦参碱能不同程度降低FBG,TG,TC和FFA,升高肝脏SOD,GSH-Px活性,降低MDA和ROS含量;氧化苦参碱50,100 mg·kg^(-1)组γ-GCS,HO-1 mRNA和蛋白表达均升高,氧化苦参碱组p-p38MAPK表达均降低。结果表明氧化苦参碱能通过抑制p38MAPK磷酸化水平减轻氧化应激,改善高脂诱导小鼠的胰岛素抵抗。

This paper was aimed to investigate the effect of oxymatrine on fat-induced insulin resistance mice （ IR）, and to explore the effects of oxymatrine on oxidative stress and on p38 mitogen activated protein kinase （p38MAPK） pathway. ApoE-/-mice 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^-1 group. C57BL/6J mice were selected as the normal control group. Mice were garage for 8 weeks. Fasting blood glucose （FBG） , cho- lesterol （TC） , triglyceride （TG） , fatty acid （FFA） and serum insulin （FINS） in the plasma were detected. Activity of superoxide dismutase （SOD）, glutathione peroxidase, glutathione peroxidase （GSH-Px） and content of malondialdchyde （MDA） in liver were detected. Reactive oxygen species （ROS） content in liver cells were detected by Flow cytometry. The expression of heine oxygenase-1 （ HO-1 ） , γ-glutamyl cysteine synthetase （γ-GCS） of liver was examined by Real time PCR and Western blot. The protein expression of p38MAPK, p-p38MAPK was examined by Western blot. In the study, the authors found that oxymatrine reduced the levels of FBG, TC, TG and FFA, increased SOD and GSH-Px contents, decreased MDA and ROS content. Compared with model group, HO-1, T-GCS mRNA and protein expression significantly increased in 50, 100 mg ·kg^-1 oxymatrine group. The expression of p-p38MAPK decreased in oxymatrine group. The results showed that oxymatrine alleviate oxidative stress in hepatic by inhibiting the phosphorylation of p38MAPK, to ameliorate fat-induced insulin resistance mice.