氧化苦参碱对高脂诱导胰岛素抵抗小鼠肝脏脂肪酸氧化的影响  

Effect of Oxymatrine on Fatty Acid Oxidation in Hepatic of Fat-Induced Insulin Resistance Mice

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：《中国中西医结合杂志》2017年第11期1351-1355,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家重点基础研究发展计划(973计划)项目(No.2012CB518606);河北省重大医学科研项目(No.zd2013002;No.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脂肪酸氧化的影响。方法72只ApoE-/-小鼠高脂喂养16周制备胰岛素抵抗模型,随机分为模型组、氧化苦参碱25、50、100mg/kg组,每组18只,18只C57BL/6J小鼠设为对照组,氧化苦参碱各剂量组相应氧化苦参碱灌胃8周。对照组及模型组给予同体积的纯净水。高胰岛素-正葡萄糖钳夹试验评价胰岛素抵抗程度,测定葡萄糖输注率(GIR);测定血清和肝脏游离脂肪酸(FFA)含量;测定FBG、TC、TG、FINS水平,计算胰岛素抵抗指数(HOMA-IR);实时荧光定量PCR(qRT-PCR)和Western blot检测肝组织脂肪酸氧化调控因子[过氧化物酶体增殖物激活受体α(PPARα)、细胞色素P4502E1(CYP2E1)、细胞色素P4504A1(CYP4A10)]、脂肪酸氧化限速酶[肉毒碱棕榈酰基转移酶1(CPT1)、细胞色素氧化酶(COX1)、解偶联蛋白2(UCP2)]的表达。结果与对照组比较,模型组小鼠体重、血清FBG、TC、TG、FINS水平、HOMA-IR值、血清和肝脏中FFA含量均明显升高(P<0.05),GIR明显降低(P<0.05),PPARα、CYP2E1、CYP4A10及CPT1mRNA和蛋白表达降低(P<0.05),COX1及UCP2mRNA和蛋白表达升高(P<0.05)。与模型组比较,氧化苦参碱25mg/kg组TC、TG和HOMA-IR值降低(P<0.05),氧化苦参碱50mg/kg组血清FBG、TC、TG、FINS水平和HOMA-IR降低(P<0.05),氧化苦参碱100mg/kg组体重、血清FBG、TC、TG、FINS水平和HOMA-IR均降低(P<0.05),氧化苦参碱50、100mg/kg组GIR明显升高(P<0.05)。与模型组比较,氧化苦参碱各剂量组肝脏PPARα、CYP2E1、CYP4A10及CPT1mRNA和蛋白表达升高(P<0.05),COX1及UCP2mRNA和蛋白表达以及血清和肝脏中FFA含量均降低(P<0.05)。结论氧化苦参碱通过调节肝脏FFA氧化,改善高脂诱导小鼠的胰岛素抵抗。Objective To investigate the effects high fat diet induced insulin resistance mice. Methods of oxymatrine on fatty acid oxidation in liver of 72 ApoE-/- mice fed with high fat diet for 16 weeks to construct insulin resistance model were randomly divided into the model group and Oxymatrine 25, 50, 100 mg/kg groups, 18 in each group. Eighteen C57BL/6J mice were recruited as the control group. Then the mice were administered with appropriate oxymatrine by gastrogavage for 8 weeks in each dose group of oxymatrine, equal volume of pure water to the control and model group. Hyper insulinemic- euglycemic clamp test was used to evaluate insulin resistance of mice, while the glucose infusion rate （GIR） was measured. The levels of free fatty acid （FFA） in the serum and hepatic tissues, FBG, TC, TG and FINS were detected, while the insulin resistance index （HOMA-IR） was calculated. The expression lev- els of fatty acid oxidation regulators [peroxisome proliferator-activated receptor α （PPARα）, cytochrome P4502E1 （CYP2E1）, cytochrome P4504A1 （CYP4A10）], fatty acid oxidation rate-limiting enzyme [carni- tine palmitoyl transferase 1 （CPT1）, cytochrome oxidase （COX1） and solution uncoupling protein 2 （UCP2） ] in liver tissues were examined by Real-time reverse transcription PCR （qRT-PCR） and Western blot. Results Compared with the control group, the body weight, serum FBG, TC, TG, FINS, HOMA-IR value, serum and liver FFA content increased significantly （P 〈0.05）, while GIR decreased in the model group （P 〈0.05）. The mRNA and protein expression levels of PPARα, CYP2A1, CYP4A10 and CPT1 de- creased （P 〈0.05）, while COX1 and UCP2 increased in the model group （P 〈0.05）. Compared with the model group, the levels of TC, TG and HOMA-IR decreased in oxymatrine 25 mg/kg group （P 〈0.05）, while the levels of FBG, TC, TG, FINS and HOMA-IR increased in oxymatrine 50 mg/kg group （P 〈0.05）. The lev- els of weight, FBG, TC, TG, FINS and HOMA-IR decreased in oxymatr

关 键 词：氧化苦参碱 高脂饮食 胰岛素抵抗 脂肪酸氧化 

分 类 号：R285.5[医药卫生—中药学]