摘要
目的 阐明盐酸小檗碱 (berberinechloride ,Ber)及其与环孢素A (cyclosporin ,CsA)合用对大鼠肝脏P4 5 0同工酶和多药耐药基因的影响。方法 采用分光光度法测定大鼠肝微粒体红霉素N 脱甲基酶 (ERD)、氨基比林N 脱甲基酶(ADM )的活性 ,采用RT PCR法测定大鼠肝脏CYP3A1、CYP1A1、CYP2E1、mdr1a和mdr1b基因的水平。结果 灌胃给药 6d后 ,除外 10 0mg·kg-1Ber组 ,其余各组对ERD活性有明显的抑制作用 ;给药 12d时 ,所有用药组对ERD活性均有抑制作用。给药 6d后 ,CsA单用组、Ber与CsA合用组对ADM均有抑制作用 ;给药 12d后 ,除了 15 0mg·kg-1酮康唑组和 10 0mg·kg-1Ber组外 ,其余各用药组对ADM均有抑制作用。给药 12d时 ,除了 10 0mg·kg-1Ber组外 ,其余各用药组对大鼠肝脏CYP3A1、CYP2E1、mdr1a、mdr1b基因均有抑制作用。各组的CYP1A1基因均未能检出。结论 抑制CYP3A基因的表达及酶的活性 ,抑制mdr1a、mdr1b基因的表达 ,从而减少CsA在肝脏的代谢及消除 。
AIM To study the effects of coadministration of berberine chloride(Ber) with cyclosporin (CsA) on liver microsomal cytochrome P450 isoenzyme and multi drug resistance gene in rats. METHODS The activities of liver microsomal erythromycin demethylase(ERD) and aminopyrence N demethylase(ADM) were determined. The levels of mRNA expression of CYP3A1, CYP1A1, CYP2E1, mdr1a and mdr1b were assayed with RT PCR. RESULTS After administration for 6 days, all treatment groups except Ber at 100 mg·kg -1 exhibited inhibitory action on ERD activity in rats. ERD activity markedly decreased in all drug treatment groups after taking drug for 12 days. After administration for 6 days, 45 mg·kg -1 CsA, 100 mg·kg -1 Ber coadministrated with 45 mg·kg -1 CsA and 200 mg·kg -1 Ber plus 45 mg·kg -1 CsA had significant inhibitory effects on ADM activity in rats. All groups except 100 mg·kg -1 Ber and 150 mg·kg -1 ketoconazole had the same effects on ADM activity after treatment for 12 days. Again, after 12 days, all drug treatment groups except 100 mg·kg -1 Ber group was found of remarkable inhibition of the mRNA expression of CYP3A1, CYP2E1, mdr1a and mdr1b. The CYP1A1 gene was not detected in all groups. CONCLUSION The mechanism of Ber to increase CsA concentration is that Ber decreases the expression of CYP3A, mdr1a and mdr1b thereby reduces the metabolism and elimination of CsA by liver.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2002年第4期397-401,共5页
Chinese Pharmacological Bulletin
