环孢素与小檗碱合用抑制肝CYP3A1、CYP2E1、mdr1基因表达的实验研究

An Experimental Study of the Inhibition of the Expression of CYP3A1, CYP2E1 and mdr1 Genes of the Liver by Combined Administration of Cyclosporin and Berberine Hydrochloride

目的:观察环孢素(cyclosporin,CsA)单用及与小檗碱(berberine chloride,Ber)合用对小鼠和大鼠肝CYP3Al、CYP2El基因及多药耐药基因mdrla和mdrlb表达的影响。方法:采用逆转录聚合酶链反应(RT-PCR)法测定小鼠和大鼠肝CYP3Al、CYP2El、mdrla和mdrlb基因在给药后的变化。结果:小鼠灌胃给药6 d时,Ber与CsA合用对CYP3Al和CYP2El基因均有明显抑制作用;大鼠灌胃给药12 d时,与对照组比较,除了Ber 100 mg·kg^(-1)组外,其余各组对大鼠肝CYP3Al、CYP2El、mdrla、mdrlb基因均有明显的抑制作用。结论:Ber与CsA合用可明显抑制小鼠和大鼠肝CYP3Al及mdrla、mdrlb基因的表达,从而减少CsA在肝的代谢及消除,这可能是Ber增加CsA血药浓度的重要机制。

Objective: To survey the effects of cyclosporine (CsA) used alone and in combination with berberine hydro-chloride (Ber) on the expression of CYP3A1 and CYP2E1 genes as well as the multidrug-resistant genes mdrla and mdrlb of the liver in mice and rats. Methods: The levels of the expression of CYP3A1, CYP2E1, mdr1a and. mdr1b genes in the murine liver were assayed with RT-PCR after the drug administration. Results: 6 days after the combined medication of Ber and CsA administered by gastrogavage in mice, the expression of CYP3A1 and CYP2E1 genes in the liver was markedly inhibited. 12 days after the administration of the drugs given by gastrogavage in rats, the expression of CYP3A1, CYP2E1, mdr1a and mdr1b genes of the liver was all significantly inhibited except that Ber 100 mg·kg^(-1) used alone had not such an effect. Conclusion: Comlined application of Ber and CsA was shown to inhibit significantly the expression of CYP3A1, CYP2E1, mdr1a and mdr1b genes of the liver in mice and rats, thereby decreasing the catabolic elimination of CsA in the liver, This may be the important mechanism for Ber to increase the blood concentration of CsA.