摘要
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。
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 divid- ed into 5 groups ： normal diet ＋ pretreatment of solvent （ ND ） ; high-fat diet ＋ pretreatment of solvent （HFD） ;high-fat diet ＋ pretreatments of either lovas- tatin （LD） or Bet low dose （BLD） and Ber high dose （BHD）. The levels of total cholesterol （ TC ）, trigly- eride （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 sig- nificantly 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 Bet showed feedback down regulation to In- sig-2 gene expression. Conclusions Ber can signifi- cantly decrease the levels of blood-lipids of the hyper- lipidemic rats, the mechanism of which ,nay be related to elevating expressions of Insig-2 gene in liver. As a result, the cholesterol synthesis of liver can be inhibited.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2009年第1期85-88,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30600812)
