8-烷基小檗碱衍生物对胆固醇代谢及低密度脂蛋白受体表达的影响

Effects of 8-alkylberberine derivatives on cholesterol metabolism and low-density lipoprotein receptor

探索了8-烷基小檗碱衍生物的浓度和碳链长度对低密度脂蛋白受体(LDLR)表达和各项降脂指标的影响。通过western blot分析不同浓度8-烷基小檗碱衍生物对HepG2细胞和动物肝脏中LDLR的变化,同时检测动物体内各项生理指标总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)。结果表明在HepG2细胞中,随着碳链的延长,LDLR表达量增加,在所有化合物中,8-十六烷基小檗碱显示了最强的上调LDLR能力;另外,动物实验中8-烷基小檗碱衍生物治疗后血清中的指标TC、TG、LDL-C、HDL-C和肝脏LDLR也均有显著的改变。尤其是与高血脂组比较,8-十六烷基小檗碱分别降低TC、TG、LDL-C为31.9%、14.4%、21.5%,提升了HDL-C 22.8%,更重要的是8-十六烷基小檗碱能使HepG2细胞和肝脏中LDLR表达量分别增加3.3倍和2.89倍(p<0.01)。随着碳链的延长,8-烷基小檗碱衍生物比小檗碱具有更好降脂能力,尤其是8-十六烷基小檗碱通过上调LDLR表达可作为潜在的降脂药物开发。

The effects of 8-alkyl-berbefine derivatives （8-BBR-C.） on low-density lipoprotein receptor （LDLR） expression and antihyperlipidemic levels have been studied. The Western blot was used to analyze the variation of LDLR protein expression in HepG2 and liver tissues, and the levels of TC, TC, LDL-C and HDL-C were also measured. The results showed that in HepG2 cells, the expression of LDLR increased with the elongation of the aliphafic chain. Among all compounds synthesized and BBR, 8-cetyl-berberine （8-BBR-C16） was shown to obviously enhance the expression of LDLR in HepG2 cells. Further remflts in animal experiments indicated that 8-BBR-Cn treatment changed markedly the levels ofTC, TG, LDL-c and HDL-c in serum and LDLR in hamster rivers, compared with the hyperlipidemic control group; statistical analysis revealed that TC, TG, LDL-c and HDL-c decreased significantly （p〈0.01） by 31.9%, 14.4%, 21.5% and 22.8%, respectively, with 8-BBR-C16 lreatment. Moreover, LDLR protein expression was significantly increased by about 3.3-fold in HepG2 cells and 2.89-fold in livers （p〈0.01 ）. All these results demonsWated that 8-BBR-Cn with a moderate length of aliphatic chain can improve the cholesterol level better than BBR; 8-BBR-Ct6 is especially a potential compound to lower cholesterol level by adjusting the LDLR expression.