盐酸小檗碱及其与环孢素A合用对大鼠肝脏和小肠CYP3A2表达影响

 目的　阐明盐酸小檗碱(berberinehydrochloride,Ber)及其与环孢素A(cyclosporinA,CsA)合用对大鼠肝脏和小肠CYP3A2的影响。方法　实验分溶媒对照组、200mg·kg^-1Ber组、10mg·kg^-1CsA组、200mg·kg^-1Ber+10mg·kg^-1CsA组,Ber灌胃给药6d,CsA仅在实验第6天灌胃给药。采用RT-PCR和Westernblot等方法测定大鼠肝脏和小肠CYP3A2的表达水平。结果　RT-PCR结果表明,与对照组比较,各实验组对大鼠肝脏CYP3A2/β-acting的比值无明显影响;200mg·kg^-1Ber+10mg·kg^-1CsA组则可显著降低大鼠小肠CYP3A2/β-acting的比值(P <0.05);两药合用组与200mg·kg^-1Ber组相比可显著抑制CYP3A2的表达(P<0.05),与10mg·kg^-1CsA组相比则无显著差异(P>0.05)。Westernblot结果表明,与对照组比较,各实验组对大鼠肝脏CYP3A2蛋白水平的表达无明显抑制作用,但是200mg·kg^-1Ber+10mg·kg^-1CsA组则对小肠CYP3A2蛋白水平的表达有明显抑制作用(P<0.05);两药合用组与200mg·kg^-1Ber组相比可显著抑制CYP3A2的表达(P <0.05),与10mg·kg^-1CsA组相比则无显著差异(P>0.05)。结论　Ber对CsA下调小肠CYP3A2的效应至少有相加作用,是否有协同效应还需进一步研究,但是,CsA对Ber下调小肠CYP3A2有协同作用可以确立。

Effects of berberine hydrochloride and its coadministration with cyclosporin A on CYP3A2 expression in rat liver and small intestine

OBJECTIVE To study the effects of berberine hydrochloride(Ber) and its coadministration with cyclosporin A (CsA) on CYP3A2 in rat liver and small intestine.METHODS The rats were randomly divided into the following groups: control group,group administrated with 200mg·kg^-1 Ber,group administracted with 10mg·kg^-1 CsA, group coadministrated with 200mg·kg^-1 Ber and 10mg·kg^-1 CsA Ber was orally administrated once a day for 6 d and CsA was orally taken only on the sixth day. The levels of CYP3A2 in rat liver and small intestine were assayed with RT-PCR and Western blot.RESULTS RT-PCR analysis indicated that all groups had no significant inhibitory effects on the CYP3A2/β-acting ratio in rat liver, but the group coadministrated with 200 mg·kg^-1 Ber and 10 mg·kg^-1 CsA could strongly decreased the CYP3A2/β-acting ratio in rat small intestine (P <0.05). The coadministration markedly down regulated the CYP3A2 expression in rat small intestine compared with the administration of 200 mg·kg^-1 Ber(P<0.05),but it had no significant inhibitory effects on this gene compared with the administration of 10 mg·kg^-1 CsA(P >0.05).Western blot analysis showed that all administration groups had no significant inhibitory effects on the expression of CYP3A2 protein in rat liver.However, the coadministration could markedly inhibit the expression of CYP3A2 protein in rat small intestine (P<0.05). The coadministration significantly down regulated the CYP3A2 expression in rat small intestine compared with the administration of 200mg·kg^-1 Ber(P<0.05), but it had no significant inhibitory effects on this gene compared with 10 mg·kg^-1 CsA(P>0.05). CONCLUSION Ber had additive action on the down regulation effect on CYP3A2 expression induced by CsA. Whether Ber had synergistic action on this gene’s down regulation induced by CsA needed to be studied further However, it was certain that CsA had cooperative effect on the CYP3A2’s down-regulation caused by CsA.