亲脂性修饰对小檗碱体内调脂活性的影响

Influence of lipophilic structure-modification on lipid-modulating effect of berberine in vivo

目的:观察亲脂性修饰后小檗碱体内调脂活性的变化.方法:以8-烷基小檗碱同系物(Ber-n)为模型化合物,以实验性高脂血症大鼠为实验动物模型,实验分为正常对照组(NC组),高脂对照组(FC组)和小檗碱组(Ber-0组),8-丁基小檗碱组(Ber-4组),8-辛基小檗碱组(Ber-8组),8-月桂基小檗碱组(Ber-12组),8-十六烷基小檗碱组(Ber-16组)5个药物组.实验期间NC组给予普通饲料,FC组和5个药物组均给予高脂饲料.用7g/L羧甲基纤维素钠水溶液作为药物溶剂,5个药物组大鼠每日按125mg/kg分别给予灌胃相应药物,NC组和FC组给予同体积药物溶剂.于给药后10d和25d时测定各组实验大鼠血清总胆固醇(TC)、总三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)含量;实验结束时记录计算各组大鼠肝脏指数,肾脏指数,脾脏指数和胸腺指数.结果:在给药10d后与FC组相比较,各药物组血清TC,TG,HDL-C均有一定程度的修复.HDL-CBer-16组(1.22±0.19)mmol/L与FC组(0.95±0.19)mmol/L相比较差异显著(P<0.05),但各Ber-n组间的差异不明显.当给药25d后,TC值FC组(11.38±3.41)mmol/L与Ber-8组(6.77±3.26)mmol/L相比较差异显著(P<0.05),与Ber-12组(5.24±2.45)mmol/L,Ber-16组(4.78±2.67)mmol/L相比较差异更为显著(P<0.01).TG值FC组(1.05±0.37)mmol/L与Ber-12组(0.64±0.25)mmol/L,Ber-16组(0.66±0.23)mmol/L相比较差异显著(P<0.05).HDL-C值FC组(1.11±0.21)mmol/L与Ber-8组(1.34±0.20)mmol/L差异显著(P<0.05);与Ber-12组(1.49±0.21)mmol/L,Ber-16组(1.48±0.28)mmol/L相比较差异更为显著(P<0.01).各药物组的肝脏指数与FC组相比较明显降低且均有显著差异(P<0.05).结论:随着烷基链长度的增加,Ber-n对血脂异常的修复能力也随之增强,亲脂性的提高有利于小檗碱衍生物体内调脂活性的发挥.

AIM：To study the effect of lipophilic structure-modification on Lipid-modulating ability of berberine in vivo.METHODS：With 8-alkyl-berberine homologues（Ber-n）as model drug and experimentalhyperlipidemia rats as animal model,the normal control group（NC）,high fat control group（FC）and drug groups including berbreine（Ber-0）group,8-butyl-berberine（Ber-4）group,8-octyl-berberine（Ber-8）group,8-dodecyl-berberine（Ber-12）group and 8-cetyl-berberine（Ber-16）group were set up randomly.During experiment,the basic diet were supplied to NC group and high fat diet to FC group and 5 drug groups,and all drug groups were treated with corresponding drug by dose of 125 mg/kg a day respectively and NC group and FC group with drugs solvent by gavage.The serum indexes including total cholesterol（TC）,total glyceride（TG）and high density lipoprotein cholesterol（HDL-C）were determined after administrationat 10 or 25 d respectively.RESULTS：After administration at 10 d the appreciably repairing effect of all drug groups on serum indexes were observed,and the HDL-C value of Ber-8 group（1.22±0.19）mmol/L was significantly different than that of FC group（0.95±0.19）mmol/L.After administrationat 25 d,the serum TC value of Ber-8 group（6.77±3.26）mmol/L were significantly different（P〈0.05）and that of Ber-12 group（5.24±2.45）mmol/L and Ber-16 group（4.78±2.67）mmol/L were very significantly different（P〈0.01）than that of FC group（11.38±3.41）mmol/L,and the serum TG valueof Ber-12 group（0.64±0.25）mmol/L and Ber-16 group（0.66±0.23）mmol/L both were significantly different（P〈0.05）than that of FC group（1.05±0.37）mmol/L,and the serum HDL-C value of Ber-8 group（1.34±0.20）mmol/L were significantly different（P〈0.05）and that of Ber-12 group（1.49±0.21）mmol/L and Ber-16 group（1.48±0.28）mmol/L were very significantly different（P〈0.01）than that of FC group（1.11±0.21）mmol/L.CONCLUSION：Overall analysis,the Lipid-modulating effects of Ber-n increased as the length of aliphatic chain was elongated.The lipophilic structure-modification on berberine molecule are beneficial to exerting Lipid-modulating effect in vivo.