补骨脂酚对小鼠肝功能和胆汁酸转运体BSEP、NTCP的影响

Influence of Bakuchiol on liver function and bile acid transporters BSEP and NTCP in mouse

[目的]观察补骨脂酚对小鼠肝功能和胆汁酸转运体胆盐输出泵(BSEP)、钠牛磺酸胆酸共转移蛋白(NTCP)的影响。[方法]小鼠连续14 d皮下注射50 mg/kg补骨脂酚和10 mg/kgα-雌二醇,分别在给药1、3、7、14 d后处死部分小鼠取材,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,取新鲜肝脏用酶联免疫吸附法(ELISA法)检测BSEP、NTCP的蛋白表达。[结果]补骨脂酚和α-雌二醇对小鼠体质量没有明显影响。α-雌二醇皮下注射14 d会使小鼠血清谷丙转氨酶(ALP)升高、肝脏肿大、肝系数升高,而补骨脂酚无此作用,但给药期间补骨脂酚可导致血清ALP一过性降低,14 d时恢复正常。补骨脂酚对肝脏BSEP基本没有影响,而会导致NTCP逐渐升高,给药14 d时NTCP显著高于溶剂组。给药14 d,补骨脂酚组小鼠肝脏无病变,而α-雌二醇组小鼠肝脏存在肝细胞变性。[结论]50 mg/kg补骨脂酚给药14 d未见肝脏毒性,而10 mg/kgα-雌二醇肝毒性明显。

[Objective] To observe the influence of bakuchiol on liver function and bile acid transporters in mice.[Methods] Mice were treated with 50 mg/kg Bakuchiol and 10 mg/kg-estradiol continuously for 14 d. At 1, 3, 7 and 14 d, mice were divided into several parts to kill. The material from mice killed was for serum biochemical indicators testing. Then mice livers were taken weight and carry on the liver histologic examination and take fresh liver to detect BSEP, NTCP protein expression with ELISA method. [Results] Bakuchiol and α-estradiol had no significant effect on body weight in mice. The subcutaneous injection of α-estradiol for 14 d made mice elevated serum ALP, hepatomegaly, liver coefficient increased, but the Bakuchiol didn＇t. ALP decreased for the time of the Bakuchiol injection, after 14 d back to normal. Bakuchiol had no effect on the liver BSEP mostly, and would result in higher NTCP gradually, for 14 d NTCP group was significantly higher than the solvent. After 14 d treatment, Bakuchiol groups of mice liver lesions, and α-estradiol group mice liver had cell degeneration. [Conclusion] Bakuchiol treatment for 14 d does not induce liver injury, but hepatotoxicity of α-estradiol is obvious.