CAJ | 학술논문

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-C22.8%,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.
탐색료8-완기소벽감연생물적농도화탄련장도대저밀도지단백수체(LDLR)표체화각항강지지표적영향.통과western blot분석불동농도8-완기소벽감연생물대HepG2세포화동물간장중LDLR적변화,동시검측동물체내각항생리지표총담고순(TC)、감유삼지(TG)、저밀도지단백(LDL-C)화고밀도지단백(HDL-C).결과표명재HepG2세포중,수착탄련적연장,LDLR표체량증가,재소유화합물중,8-십륙완기소벽감현시료최강적상조LDLR능력;령외,동물실험중8-완기소벽감연생물치료후혈청중적지표TC、TG、LDL-C、HDL-C화간장LDLR야균유현저적개변.우기시여고혈지조비교,8-십륙완기소벽감분별강저TC、TG、LDL-C위31.9%、14.4%、21.5%,제승료HDL-C22.8%,경중요적시8-십륙완기소벽감능사HepG2세포화간장중LDLR표체량분별증가3.3배화2.89배(p<0.01).수착탄련적연장,8-완기소벽감연생물비소벽감구유경호강지능력,우기시8-십륙완기소벽감통과상조LDLR표체가작위잠재적강지약물개발.
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 significantly (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 livers (p<0.01). All these results demonstrated that 8-BBR-Cn with a moderate length of aliphatic chain can improve the cholesterol level better than BBR; 8-BBR-C16 is especially a potential compound to lower cholesterol level by adjusting the LDLR expression.