氧化苦参碱对高脂诱导胰岛素抵抗ApoE^(-/-)小鼠肝脏脂代谢相关基因的影响  

Effect of oxymatrine on lipid metabolism regulated genes in liver of fat-induced insulin resistance in Apo E^(-/-) mice

作　　者：王杏[1] 王超[1] 宋光耀[2] 费雯婕 刘小娜[2] 张哲[1] 马欢[1] 

机构地区：[1]河北省人民医院老年医学重点实验室,河北石家庄050051 [2]河北省人民医院内分泌科,河北石家庄050051

出　　处：《中国药理学通报》2015年第12期1688-1692,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81370900);河北省重大医学科研项目(No zd2013002;zd2013004)

摘　　要：目的探讨氧化苦参碱对高脂诱导胰岛素抵抗Apo E^(-/-)小鼠肝脂代谢相关基因的影响。方法 17只♂C57BL/6J小鼠作为对照组,给予正常饮食;68只♂Apo E^(-/-)小鼠,给予高脂饮食,饲养16周后,将小鼠分为模型组、氧化苦参碱低、中、高剂量组。给药8周,测定小鼠体重和一般生化指标。荧光定量PCR和Western blot方法检测肝组织LPL、FAT/CD36、CPT1、UCP2、SREBP-1c、FAS、ACC m RNA和蛋白表达水平。结果氧化苦参碱能不同程度的降低体重、FBG、TC、TG、FFA、FINS、HOMA-IR,升高GIR,改善胰岛素的抵抗。同时降低了LPL、FAT/CD36、UCP2、SREBP-1c、FAS、ACC m RNA和蛋白的表达水平,升高了CPT1表达水平。结论氧化苦参碱能够通过脂转运、氧化、合成3个环节较全面的调节肝脂质代谢,改善高脂诱导的Apo E^(-/-)小鼠的胰岛素抵抗。Aim To investigate the effect of oxymatrine on lipid metabolism regulated genes in liver in fat-induced insulin resistance in Apo E^(-/-)mice. Methods Seventeen C57 BL /6J male mice were selected in normal control group. Sixty-eight Apo E^(-/-)mice with high fat diet for 16 weeks,were randomly divided into model group,oxymatrine low,middle and high dose groups. Then they were gavaged for 8 weeks. Body weight and general biochemical indicators were determined in mice. The m RNA and protein expression levels of LPL,FAT / CD36,CPT1,UCP2,SREBP-1c,FAS and ACC were examined by real-time PCR and Western blot in the liver. Results Compared with model group,oxymatrine reduced body weight( BW),fasting blood glucose( FBG),cholesterol( TC),triglyceride( TG),free fatty acids( FFA),fasting plasma insulin( FINS) and insulin resistance index( HOMA-IR)( P <0. 05),while improved glucose infusion rate( GIR).Oxymatrine down-regulated the m RNA and protein expression of LPL,FAT / CD36,UCP2,SREBP-1c,FAS and ACC( P < 0. 05),and up-regulated the m RNA and protein expression of CPT1 in varying degrees( P <0. 05). Conclusion Oxymatrine can regulate the expression of lipid metabolism regulated genes in liver and improve insulin resistance in Apo E^(-/-)mice induced by high fat diet.

关 键 词：氧化苦参碱 高脂 APOE^-/-小鼠 胰岛素抵抗 脂代谢 肝脏 

分 类 号：R-332[医药卫生] R284.1