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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 study was designed to investigate the effects of oxymatrine on high fat-induced insulin resistance (IR) mice and its effects on hepatic oxidative stress and p38 mitogen-activated protein kinase (p38MAPK) pathway in IR mice. The experimental high-fat diet Apo E - / - mice 16 weeks as the IR model, random number table divided into four groups, namely, insulin resistance group, oxymatrine low, medium and high doses (25,50,100 mg · kg ~ (-1)) group. C57BL / 6J mice were given as control group and were given gavage for 8 weeks. The content of blood glucose (FBG), triglyceride (TG), cholesterol (TC), fatty acid (FFA) and insulin (FINS) were measured. The levels of superoxide dismutase (SOD), glutathione peroxidase GSH-Px activity and malondialdehyde (MDA) were detected by flow cytometry. The levels of reactive oxygen species (ROS) in hepatocytes were detected by flow cytometry. The levels of heme oxygenase-1 (HO- , Γ-glutamylcysteine synthetase (γ-GCS) expression; Western blot determination of p38MAPK, p-p38MAPK protein expression. The study found that oxymatrine can reduce FBG, TG, TC and FFA to some extent, increase the activities of SOD and GSH-Px in the liver and decrease the content of MDA and ROS; GCS, HO-1 mRNA and protein expression were increased, oxymatrine group p-p38MAPK expression were reduced. The results showed that oxymatrine can reduce oxidative stress by inhibiting the phosphorylation of p38MAPK and improve insulin resistance in mice induced by high fat diet.