Wang Chao, Zhang Hui-Xin, Xing Han-Ying, Wang Xing, Zhang Zhe
Hebei General Hospital, Key Laboratory of Geriatrics, Shijiazhuang 050051, China.
Hebei Yiling Medicine Institution, Pharmacology Department, Shijiazhuang 050035, China.
Zhongguo Zhong Yao Za Zhi. 2016 Aug;41(15):2872-2876. doi: 10.4268/cjcmm20161521.
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 gavage for 8 weeks. Fasting blood glucose (FBG), cholesterol (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 malondialdehyde (MDA) in liver were detected. Reactive oxygen species (ROS) content in liver cells were detected by Flow cytometry. The expression of heme 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, γ-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.
本文旨在研究氧化苦参碱对高脂诱导的胰岛素抵抗小鼠（IR）的影响，并探讨氧化苦参碱对氧化应激及p38丝裂原活化蛋白激酶（p38MAPK）通路的作用。选取给予高脂饮食16周的ApoE-/-小鼠作为IR动物模型，随机分为模型组、氧化苦参碱25、50、100 mg•kg⁻¹组。选取C57BL/6J小鼠作为正常对照组。小鼠灌胃8周。检测血浆中空腹血糖（FBG）、胆固醇（TC）、甘油三酯（TG）、脂肪酸（FFA）及血清胰岛素（FINS）。检测肝脏中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性及丙二醛（MDA）含量。采用流式细胞术检测肝细胞内活性氧（ROS）含量。通过实时荧光定量PCR和蛋白质免疫印迹法检测肝脏中血红素加氧酶-1（HO-1）、γ-谷氨酰半胱氨酸合成酶（γ-GCS）的表达。采用蛋白质免疫印迹法检测p38MAPK、磷酸化p38MAPK（p-p38MAPK）的蛋白表达。研究中，作者发现氧化苦参碱降低了FBG、TC、TG和FFA水平，增加了SOD和GSH-Px含量，降低了MDA和ROS含量。与模型组相比，50、100 mg•kg⁻¹氧化苦参碱组HO-1、γ-GCS mRNA和蛋白表达显著增加。氧化苦参碱组p-p38MAPK表达降低。结果表明，氧化苦参碱通过抑制p38MAPK磷酸化减轻肝脏氧化应激，从而改善高脂诱导的胰岛素抵抗小鼠。
