黄连碱对胆固醇代谢关键基因的调节作用  

Regulatory effect of coptisine on key genes involved in cholesterol metabolism

作　　者：陈彪[1] 薛东芳[1] 韩冰[1] 寇淑鸣 叶小利[1,2] 李学刚[3,2,4] 

机构地区：[1]西南大学生命科学学院,重庆400715 [2]现代生物医药研究所,重庆400715 [3]西南大学药学院,重庆400715 [4]重庆药物过程与质量控制工程技术研究中心,重庆401122

出　　处：《中国中药杂志》2015年第8期1548-1553,共6页China Journal of Chinese Materia Medica

基　　金：国家科技支撑计划项目(2011BAI13B02-1);高等学校博士学科点专项科研基金项目(20130182110023);重庆市百名高端工程技术人才计划(2013-2016);西南大学县校合作创新基金项目(Sz201401;Sz201302)

摘　　要：该文主要研究胆固醇和25-羟胆固醇诱导对HepG2细胞胆固醇代谢的影响和黄连中黄连碱的降胆固醇活性及调节机制。用生化法检测了总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-c)和高密度脂蛋白-胆固醇(HDL-c)水平;用qRT-PCR和Western bolt技术检测了胆固醇代谢关键基因LDLR,HMGCR,CYP7A1mRNA和蛋白的表达水平。结果显示胆固醇和25-羟基胆固醇诱导能导致LDLR,CYP7A1的muRNA和蛋白的表达下降从而使TC和LDL-c含量上升。黄连碱能上调LDLR和CYP7A1的muRNA和蛋白表达水平而下调HMGCR的mRNA和蛋白表达水平,从而降低TC,LDL-c水平。这些结果表明黄连碱具有潜在的降胆固醇的药理活性,其分子机制可能是通过调节胆固醇代谢的关键基因LDLR,CYP7A1和HMGCR的mRNA和蛋白表达而达到降胆固醇的效果。该研究为开发新的具有降胆固醇活性的天然药物奠定了良好的理论基础。To study the effect of cholesterol and 25-OH-cholesterol on cholesterol metabolism in HepG2 cells and the effect of cop- tisine （Cop） extracted from Coptidis Rhizoma （CR） in reducing and regulating cholesterol. In this study, TC, TG, LDL-c and HDL- c were measured by biochemical analysis; mRNA and protein expressions of LDLR, HMGCR and CYP7A1 were detected by qRT-PCR and Western blot. According to the results, cholesterol and 25-OH-cholesterol inducing could decrease in mRNA and protein expres- sions of LDLR and CYP7A1, so as to increase TC and LDL-c contents. However, Cop could up-regulate mRNA and protein expres- sions of LDLR and CYP7A1 and down-regulate that of HMGCR, so as to reduce TC and LDL-c levels. These findings suggested that Cop has potential pharmacological activity for reducing cholesterol, and may reduce cholesterol by regulating mRNA and protein expres- sions of key genes involved in cholesterol metabolism, such as LDLR, CYPTA1 and HMGCR. This study laid a firm theoretical founda- tion for developing new natural drugs with the cholesterol-lowering activity.

关 键 词：黄连碱 胆固醇代谢 25-OH—cholesterol LDLR HMGCR CYP7A1 

分 类 号：R285.5[医药卫生—中药学]