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.doc

  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 摘要：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)，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。 关键词：8-烷基小檗碱；LDLR；胆固醇；蛋白表达 中图分类号：R963 文献标识码：A  Effects of 8-alkylberberine derivatives on cholesterol metabolism and low-density lipoprotein receptor Shi Qing1, Li Xuegang2, Shu Hejing1, He Kai1, Ye Xiaoli1 (1. College of Life Science, Southwest University, Chongqing 400715, China; 2. College of Pharmacy, Southwest University, Chongqing 400716, China) Abstract: The effects of 8-alkyl-berberine derivatives (8-BBR-Cn) 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, TG, 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 aliphatic 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 results in animal experiments indicated that 8-BBR-Cn treatment changed markedly the levels of TC, TG, LDL-c and HDL-c in serum and LDLR in hamster livers, compared with the hyperlipidemic control group; statistical analysis revealed that TC, TG, LDL-c and HDL-c decreased signi?cantly (p<0.01) by 31.9%, 14.4%, 21.5% and 22.8%, respectively, with 8-BBR-C16 treatment. Moreover, LDLR protein expression was significantly increased by about 3.3-fold in HepG2 cells and 2.89-fold in