氢溴酸槟榔碱体内对大鼠肝肾转运体表达的影响

Effect of arecoline hydrobromide on m RNA expression of hepatic and renal transporters in vivo

目的探究氢溴酸槟榔碱对大鼠肝肾转运体表达的影响。方法通过给雄性Wistar大鼠ig氢溴酸槟榔碱(0.8、4、20 mg/kg)21 d,应用荧光RT-PCR检测肝、肾组织中13种转运体m RNA的表达量,考察氢溴酸槟榔碱对大鼠肝、肾转运体m RNA表达的影响。结果氢溴酸槟榔碱低剂量时显著抑制了肝脏MRP2和MDR1A m RNA表达,但显著诱导了肾脏MRP5 m RNA表达。氢溴酸槟榔碱高剂量时显著抑制了肝脏OCT2、OAT2、OCTN2、OATP1A1、OATP1A4、OATP2B1、MRP2和MDR1A,以及肾脏MRP2、BCRP、MDR1A的m RNA表达水平,但显著上调了肾脏OCTN2、OATP1A1、OATP1A4及MRP5的m RNA表达量,且对上述转运体m RNA表达的影响有一定剂量依赖性。结论由于肝肾转运体表达与功能的改变会引起药物相互作用,临床上应给予槟榔嗜好者更多关注,以避免发生不良药物相互作用。

Objective To explore the effect of arecoline hydrobromide（AH） on the expression of rat hepatic and renal transporters. Methods The effect of AH on the m RNA expression of 13 hepatic and renal transporters was studied after orally giver AH（0.8, 4, and 20 mg/kg/d） to rats for 21 d. Results The results from the real-time PCR indicated that, AH treatment at low dose significantly decreased the m RNA levels of hepatic MRP2 and MDR1 A, while significantly increased renal MRP5 m RNA level. On the other hand, AH treatment at high dose significantly inhibited the m RNA expression of hepatic OCT2, OAT2, OCTN2, OATP1A1, OATP1A4, OATP2B1, MRP2, and MDR1 A, as well as renal MRP2, BCRP, and MDR1 A. However, the m RNA expression of renal OCTN2, OATP1A1, OATP1A4, and MRP5 were significantly up-regulated following the treatment of high dose of AH. And the AH-induced effect on the above transporters was dose dependent in some extent. Conclusion Due to the drug interaction caused by the alteration in expression and function of hepatic and renal transporters, it is suggested that the betel nut addicts should be paid more attention in case of adverse drug interactions.