小檗碱对胆固醇代谢及肝脏Insig-2基因表达的影响

目的研究小檗碱(berberine,Ber)对高脂模型大鼠胆固醇代谢的影响,并探讨其可能的机制是否与胰岛素诱导基因-2(insulin-induced gene 2,Insig-2)基因表达有关。方法♂清洁级SD大鼠40只,随机分为普食组(Normal diet,ND)、高脂饲料组(High fat diet,HFD)、高脂饲料+洛伐他汀组(Lovastatin diet,LD)、高脂饲料+低剂量小檗碱干预组(Berlow dose diet,BLD)、高脂饲料+高剂量小檗碱干预组(Berhigh dose diet,BHD)。Ber干预18 wk后测定大鼠血清总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)等血生化指标的含量。RT-PCR和Western blot技术检测各组大鼠肝脏Insig-2 mRNA和蛋白表达变化。结果Ber干预呈剂量依赖性降低高脂模型大鼠血清TC和LDL-C水平;低剂量Ber明显上调高脂血症大鼠肝脏Insig-2基因mRNA和蛋白表达水平,而高剂量Ber则反馈性下调Insig-2基因mRNA和蛋白的表达。结论Ber干预具有明显的调血脂作用,其机制可能是通过上调肝脏Insig-2基因表达,从而抑制肝脏中胆固醇的合成代谢。

Effects of berberine on cholesterol metabolism and Insig-2 gene expression of hyperlipidemic rats

Aim To investigate the effects of berberine(Ber) on cholesterol metabolism of hyper-lipidemic rats,and to explore whether its mechanism was involved in the insulin-induced gene 2(Insig-2) gene expressions in liver.Methods SD rats were randomly divided into 5 groups:normal diet + pretreatment of solvent(ND);high-fat diet + pretreatment of solvent(HFD);high-fat diet + pretreatments of either lovastatin(LD) or Ber low dose(BLD) and Ber high dose(BHD).The levels of total cholesterol(TC),triglyeride(TG),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol (HDL-C) in blood were detected eighteen weeks after rats were fed with high-fat diet and pretreated with solvent or drugs.The mRNA and protein expressions of Insig-2 in rat liver were quantified by RT-PCR and Western blot.Results The blood levels of TC and LDL-C were significantly lower in Ber groups than those in HFD;Low dose Ber pretreatment significantly increased Insig-2 gene mRNA and protein expressions in rat liver but high dose Ber showed feedback down regulation to Insig-2 gene expression.Conclusions Ber can significantly decrease the levels of blood-lipids of the hyperlipidemic rats,the mechanism of which may be related to elevating expressions of Insig-2 gene in liver.As a result,the cholesterol synthesis of liver can be inhibited.