摘要
目的观察补骨脂水提物对小鼠的肝毒性及对胆汁酸转运体的影响。方法补骨脂水提物连续ig给药4周,禁食不禁水12 h,麻醉动物后取血检测血清生化,剖取肝脏称质量并进行肝脏病理组织学检查。肝脏匀浆后ELISA法检测胆盐输出泵(BSEP)和钠离子-牛磺胆酸共转运蛋白(NTCP)蛋白的表达情况。结果补骨脂水提物以大剂量ig给药,连续给药2周80 g生药/kg组小鼠体质量显著降低,给药3周3个剂量组小鼠体质量均显著降低。给药期间,80 g生药/kg组小鼠死亡10只,40 g生药/kg组小鼠死亡6只。给药4周结束补骨脂水提物80 g生药/kg和40 g生药/kg组小鼠肝系数显著大于对照组。补骨脂水提物80 g生药/kg组雄性小鼠ALT高于对照组,雌性小鼠ALP低于对照组,40 g生药/kg组雌雄小鼠ALP均低于对照组。补骨脂水提物可使小鼠肝脏出现肿胀变性。补骨脂水提物20 g生药/kg可导致肝脏BSEP和NTCP均显著降低。结论补骨脂水提物大剂量ig给药对小鼠肝毒性明显,并可影响胆汁酸转运体的表达。
Objective To investigate the hepatoxicity of aqueous extract from Psoralea corylifolia and its effect on bile acid transportation in mice. Methods The aqueous extract from P. corylifolia was given by ig administration for 4 weeks. After fasting for 12 h, mice were anesthetized. The biochemical indices in serum, liver weight, and, histopathological examination were observed. The protein expression of bile saltexport pump（BSEP） and sodium taurocholate cotransporting polypeptide（NTCP） in liver homogenate was detected by ELISA methods. Results The aqueous extract from P. corylifolia in large-doses（80 g crude drug/kg） group was given by ig administration for 2 weeks, the body weight of mice was significantly decreased, continuous ig administration for 3 weeks, the body weight of mice in all three groups was significantly decreased. During the drug administration, ten mice died in 80 g crude drug/kg group and six mice died in 40 g crude drug/kg group. Ig administration for 4 weeks, the liver coefficients of mice in 80 g crude drug/kg group and 40 g crude drug/kg group were significantly larger than those of mice in the control group. In the 80 g crude drug/kg group, the ALT of male mice was higher than that of mice in the control group; The ALP of female mice was lower than that of mice in the control group： In the 40 g/kg group, the ALP of both male and female mice was lower than that of mice in the control group. The aqueous extract from P. corylifolia could make the degeneration of liver swelling of mice. The BSEP and NTCP in liver were significantly decreased in 20 g crude drug/kg group. Conclusion The aqueous extract from P. corylifolia in large dose group could lead the liver injury in mice and influence the expression of bile acid transporter.
出处
《药物评价研究》
CAS
2015年第3期267-270,共4页
Drug Evaluation Research
基金
重大新药创制专项项目(2011ZX09201-201-21)
国家自然基金项目(81202991)
关键词
补骨脂
肝毒性
小鼠
BSEP
NTCP
Psoralea corylifolia L.
hepatotoxicity
mouse
bile saltexport pump
sodium taurocholate cotransporting polypeptide
