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

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。

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

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.