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  

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

作　　者：辛华雯[1] 吴笑春[1] 李罄[1] 余爱荣[1] 仲明远[1] 张勤[1] 朱敏[1] 刘幼英[1] 

机构地区：[1]广州军区武汉总医院临床药理科,湖北武汉430070

出　　处：《中国药学杂志》2005年第5期353-356,共4页Chinese Pharmaceutical Journal

基　　金：湖北省自然科学基金资助课题 (2 0 0 2AB114 )

摘　　要：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、2 0 0mg·kg-1Ber组、10mg·kg-1CsA组、2 0 0mg·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 ;2 0 0mg·kg-1Ber +10mg·kg-1CsA组则可显著降低大鼠小肠CYP3A2 / β acting的比值 (P <0 .0 5 ) ;两药合用组与 2 0 0mg·kg-1Ber组相比可显著抑制CYP3A2的表达 (P<0 .0 5 ) ,与 10mg·kg-1CsA组相比则无显著差异 (P >0 .0 5 )。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 2 0 0mg·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 .0 5 ) ;两药合用组与 2 0 0mg·kg-1Ber组相比可显著抑制CYP3A2的表达 (P <0 .0 5 ) ,与 10mg·kg-1CsA组相比则无显著差异 (P >0 .0 5 )。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?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 200 mg &middot kg-1 Ber, group administracted with 10 mg &middot kg-1 CsA, group coadministrated with 200 mg &middot kg-1 Ber and 10 mg &middot 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 &middot kg-1 Ber and 10 mg &middot kg-1 CsA could strongly decreased the CYP3A2/β-acting ratio in rat small intestine (P -1 Ber (P -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 -1 Ber (P -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.

关 键 词：盐酸小檗碱 环孢素A 细胞色素P450酶 逆转录聚合酶链反应 

分 类 号：R963[医药卫生—微生物与生化药学]