小檗碱对高脂血症兔脂代谢及肝脏LDLR和SR-B1基因表达的影响  

Effect of Berberine on Lipid Metabolism and Expressions of Low Density Lipoprotein Receptor and Scavenger Receptor Class-B Type 1 Genes in Livers of Hyperlipidemic Rabbits

作　　者：金磊[1] 何琦[1] 周岐新[1] 杨俊霞[1] 

机构地区：[1]重庆医科大学药理学教研室重庆市生物化学与分子生物学重点实验室,重庆400016

出　　处：《中国生物制品学杂志》2010年第11期1226-1229,1234,共5页Chinese Journal of Biologicals

基　　金：国家自然科学基金资助项目(30600812)

摘　　要：目的研究小檗碱(Berberine,Ber)对高脂血症兔脂代谢及肝脏低密度脂蛋白受体(Low density lipoprotein re-ceptor,LDLR)和B类1型清道夫受体(Scavenger receptor B1,SR-B1)基因表达的影响。方法取新西兰大耳白兔40只,以基础饲料喂养1周后,随机选取8只为普通饲料组(ND),继续以基础饲料喂养;其余32只以高脂饲料喂养;复制高脂血症兔模型。建模8周后,将模型动物随机分为4组:高脂饲料组(HFD)、高脂饲料+非诺贝特组(FD)、高脂饲料+低剂量Ber干预组(BLD)组和高脂饲料+高剂量Ber干预组(BHD),继续喂养8周,采用全自动生化分析仪测定兔血清总胆固醇(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)的含量;观察肝脏组织病理学变化;实时荧光定量PCR法检测肝脏组织LDLR和SR-B1基因表达的变化。结果 HFD组TC、TG和LDL-C的表达水平较ND组明显升高(P<0.01),肝脏发生中度脂肪变性和水样变性的病理学改变,而经Ber干预后,血清中TC、TG和LDL-C的表达的水平较HFD组显著降低(P<0.01),且肝细胞脂肪变性和水样变性程度较HFD组有所减轻;HFD组LDLR和SR-B1基因mRNA的表达水平明显低于ND组(P<0.01),经Ber干预后,LDLR和SR-B1基因mRNA的表达水平则较HFD组明显上调(P<0.01)。结论 Ber具有明显的调血脂作用,其作用机制可能是通过上调肝脏LDLR和SR-B1基因的表达,进而抑制肝脏中胆固醇的合成。Objective To investigate the effect of berberine（Ber）on lipid metabolism and expressions of low density lipoprotein receptor（LDLR）and scavenger receptor class-B type 1（SR-B1）genes in livers of hyperlipidemic rabbits.Methods Forty New Zealand rabbits were fed with basal forage for 1 week,of which 8 were selected as normal diet（ND）group,and the other 32 were fed with high-fat diet（HFD）to copy hyperlipidemic rabbit model.Eight weeks later,the model rabbits were randomly divided into HFD,high-fat diet ＋ fenofibrate（FD）,high-fat diet ＋ Ber at low dosage（BLD）and high-fat diet ＋ Ber at high dosage（BHD）groups and further fed for 8 weeks.The total TC,TG,LDL-C and HDL-C contents in sera of rabbits were determined by full automatic biochemical analyzer,and the histopathological changes of livers were observed.The expression levels of LDLR and SR-B1 genes in livers were determined by real-time fluorescent quantitative PCR.Results Compared with those in ND group,the TC,TG and LDL-C levels in sera of rabbits in HFD group increased significantly（P〈 0.01）,while moderate fatty and watery degenerations were observed in liver tissue.However,the serum TC,TG and LDL-C levels in BLD group decreased significantly（P 〈0.01）,while the moderate fatty and watery degenerations were relieved as compared with those in HFD group.The expression levels of LDLR and SR-B1 mRNAs in HFD group were significantly lower than those in ND group（P〈 0.01）.However,both the expressions of LDLR and SR-B1 mRNAs in BLD and BHD groups were up-regulated significantly as compared with those in HFD group（P〈 0.01）.Conclusion Ber showed significantly regulatory effect on blood fat by a potential mechanism of up-regulating the expressions of LDLR and SR-B1 genes therefore inhibiting the cholesterol synthesis in liver.

关 键 词：小檗碱 血脂代谢 受体 低密度脂蛋白 清道夫受体 B类 基因表达 

分 类 号：R285.5[医药卫生—中药学] R972.6[医药卫生—中医学]