盐酸小檗碱及其与环孢素A合用对大鼠肝脏和小肠CYP3A1的影响

目的 阐明盐酸小檗碱(berberine chloride, Ber)及其与环孢素A (cyclosporin, CsA) 合用对大鼠肝脏和小肠CYP3A1的影响。 方法 实验分7组:溶媒对照组、150mg·kg^-1酮康唑组、100 mg·kg-1 Ber组、200mg·kg-1Ber组、45 mg·kg^-1CsA组、100mg·kg^-1 Ber +45mg·kg^-1CsA 组、200 mg·kg^-1 Ber +45 mg·kg^-1 CsA 组, 采用RT-PCR 和Western blot 等方法测定大鼠肝脏和小肠CYP3A1 的表达水平。 结果 RT-PCR 结果显示:灌胃给药12 d 后, 除了100 mg·kg^-1Ber 组外, 其余各用药组对大鼠肝脏CYP3A1 基因表达均有明显的抑制作用。Western blot 结果显示:给药6 d 后,200 mg·kg^-1Ber +45 mg·kg^-1CsA 组对大鼠肝脏CYP3A1 的表达有明显抑制作用;给药12 d 后,100 mg·kg^-1Ber +45 mg·kg^-1CsA, 200 mg·kg^-1Ber +45 mg·kg^-1CsA 组对大鼠肝脏和小肠CYP3A1 的表达均有明显抑制作用。 结论 通过增强CsA 对肝脏和小肠CYP3A1 基因表达的抑制作用, 从而减少CsA在肝脏和小肠的代谢及消除, 可能是Ber 增加CsA血浓度的重要机制。

Effects of berberine chloride and co-administration with cyclosporin on CPY3A1 in rat liver and small intestine

AIM: To study the effects of berberine chloride (Ber) and co-administration with cyclosporin (CsA) on CYP3A1 in rat liver and small intestine. METHODS: The rats were randomly divided into 7 groups: control group, 150 mg·kg^-1 ketoconazole, 100 mg·kg^-1 Ber, 200 mg·kg^-1 Ber, 45 mg·kg^-1CsA, 100 mg·kg^-1Ber co-administrated with 45 mg·kg^-1CsA, and 200 mg·kg^-1 Ber co-administrated with 45 mg·kg^-1CsA.The levels of CYP3A1 in rat liver and small intestine were assayed by RT-PCR and Western blot. RESULTS: After administration for 12 d, all drug administration groups, except 100 mg·kg^-1 Ber, had significant inhibitory effects on the mRNA levels of CYP3A1 by RTPCR analysis in the liver.The analysis of Western blot showed that 200 mg·kg^-1 Ber co-administrated with 45 mg·kg^-1CsA for 6d exhibited the inhibitory action on CYP3A1 in the liver.Moreover, 100 mg·kg^-1Ber co-administrated with 45 mg·kg^-1 CsA and 200 mg·kg^-1 Ber co-administrated with 45 mg·kg^-1 CsA for 12 d could markedly inhibit the expression of CYP3A1 by Western blot analysis in both liver and small intestine. CONCLUSION: The mechanism on the increase of CsA concentration by Ber may be that Ber intensifies the inhibitory effects of CsA on CYP3A1 to reduce the metabolism and elimination of CsA in liver and small intestine.