异补骨脂素腹腔注射9d所致的C57小鼠肝损害

Study on the influence of isopsoralen on C57 mice liver injury after intraperitoneal injection for 9 days

目的检测异补骨脂素腹腔注射后小鼠肝功能和胆汁酸转运体胆盐输出泵(bile salt export pump,BSEP)、钠牛磺酸胆酸共转移蛋白(Na+/taurocholate cotransporter,NTCP)和胆固醇7α-羟化酶(cholesterol 7 a-hydroxylase,CYP7A1)的变化,确证和了解异补骨脂素造成的肝损伤及可能机制。方法小鼠连续9 d腹腔注射80和40 mg/kg异补骨脂素后处死小鼠取材,检测血清生化,剖取肝称重并进行肝病理组织学检查,取新鲜肝用蛋白质印迹法检测BSEP、NTCP和CYP7A1的蛋白表达,用酶联免疫吸附法检测低密度脂蛋白受体(low density lipoprotein receptor,LDLR)。结果小鼠腹腔注射异补骨脂素后小鼠肝脏系数显著高于对照组,生化指标天冬氨酸转氨酶(aspartate transaminase,AST)和丙氨酸转氨酶(alanine Transaminase,ALT)在80 mg/kg·bw组均升高,BSEP和NTCP在80 mg/kg·bw组下降明显,80和40 mg/kg组LDLR均明显升高,差异均有统计学意义(P<0.05)。结论腹腔注射异补骨脂素会造成肝损伤,其可能与抑制BSEP、NTCP和CYP7A1表达同时促进LDLR表达有关。

Objective To detect the influence of isopsoralen on bile salt export pump（BSEP）,Na＋/taurocholate cotransporter（NTCP） and cholesterol 7 a-hydroxylase（CYP7 A1） of liver and to confirm the liver injury and explore the potential mechanism. Methods The C57 mice were injected intraperitoneally for 9 days at the dose of 80 and 40 mg/kg·bw. At the end of the experiment,mice were sacrificed,and blood was collected to detect serum biochemical parameters. Livers were weighed and examined by histopathological method.Detecting the expression of BSEP,NTCP and CYP7 A1 by Western blot and detecting the level of low density lipoprotein receptor（LDLR） by ELISA kits. Results Liver coefficient is significantly higher than the control group after intraperitoneal injection of isopsoralen. Aspartate transaminase（AST） and alanine transaminase（ALT） of 80 mg/kg·bw group increased significantly,BSEP and NTCP of 80 mg/kg·bw group obviously decreased. LDLR in 80 and 40 mg/kg·bw groups both increased markedly（P〈0. 05）. Conclusion Intraperitoneal injection of isopsoralen can cause liver damage,which probably associated with inhibiting BSEP,NTCP and CYP7 A1 while promoting LDLR.