异补骨脂素不同时间给药对大鼠肝脏功能和转运体的影响  

Effect of isopsoralen on hepatic function and bile acid transporters in SD rats with different administration periods

作　　者：黄菊阳 王琴 毕亚男 史红[1] 王跃飞[1] 周昆[1] HUANG Ju-yang;WANG Qin;BI Ya-nan;SHI Hong;WANG Yue-fei;ZHOU Kun(Tianjin Key Lab ofPharmacology of Traditional Chinese Medicine, Tianjin 300193,China)

机构地区：[1]天津中医药大学中医药研究院天津市中药药理学重点实验室,天津300193

出　　处：《中国药理学通报》2019年第2期260-264,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81673826;81703790)

摘　　要：目的探讨补骨脂活性成分异补骨脂素不同时间灌胃给药对大鼠肝脏功能和胆汁酸转运体的影响。方法 SD大鼠随机分为对照组、异补骨脂素60 mg·kg^(-1)灌胃给药1 d组、3 d组以及7 d组。实验结束后,检测大鼠的体质量和肝重;试剂盒检测大鼠血清中ALT、AST、ALP、TBA、TC、TG、TBIL的含量;real-time PCR法检测大鼠肝脏组织中胆汁酸转运体BSEP、NTCP、MRP2、MRP4、MDR1、ABCG5、ABCG8、OSTα的水平。结果与对照组相比,异补骨脂素能明显增加肝脏的重量,不同给药时间均能引起肝脏系数的增加;异补骨脂素给药后,大鼠血清中ALT、 AST、TBA、TG、TBIL的含量明显增加,ALP没有明显变化,TC明显降低,且AST的水平在异补骨脂素灌胃给药1 d之后即有明显升高;异补骨脂素灌胃给药后,肝脏中BSEP、NTCP、MRP2、MDR1、ABCG5、ABCG8、OSTαmRNA的水平明显下降,MRP4 mRNA的水平没有明显变化。结论异补骨脂素灌胃给药1～3 d即造成肝脏的损伤作用,其作用机制可能与干扰胆汁酸转运体有关。Aim To investigate the effect of isopsoralen, the active ingredient of Psoralea corylifolia , on rat liver and bile acid transporters after oral administration for different time. Methods Rats were randomly divided into four groups: the control group and the groups treated with 60 mg·kg^-1 isopsoralen for 1, 3 or 7 days. After the experiment, the body weight and liver weight were measured. The levels of ALT, AST, ALP, TBA, TC, TG and TBIL in rat serum were examined by different kits. The mRNA levels of BSEP, NTCP, MRP2, MRP4, MDR1, ABCG5, ABCG8 and OSTα in rat liver were detected by real-time PCR. Results Compared with control group, isopsoralen could induce the increase of liver weight and liver/body weight ratio. The levels of ALT, AST, TBA, TG and TBIL significantly increased after administration of isopsoralen. The content of ALP did not change significantly and the content of TC decreased remarkably. Furthermore, the level of AST significantly increased after one day of isopsoralen administration. After treatment with isopsoralen, the mRNA levels of BSEP, NTCP, MRP2, MDR1, ABCG5, ABCG8 and OSTα were distinctly reduced. The mRNA levels of MRP4 showed no significant difference. Conclusions The administration of isopsoralen for 1 to 3 days may cause obvious liver injury. The mechanism underlying isopsoralen-induced injury may be associated with the interference of bile acid transporters.

关 键 词：大鼠 补骨脂 异补骨脂素 肝损伤 胆汁酸 转运体 

分 类 号：R332[医药卫生—人体生理学] R285.5[医药卫生—基础医学]