豚鼠耳蜗外侧壁中MDR_1基因表达与内淋巴液中ADM积聚的关系

Relationship Between Expression of MDR_1 Gene in Cochlea Lateral Wall and Accumulation of Adriamycin in Endolymph of Guinea Pig

目的 探讨豚鼠耳蜗外侧壁中多药耐药基因1 (multidruginresistancegene,MDR1 基因 )表达与耳蜗内淋巴液中阿霉素 (adriamycin ,ADM)积聚浓度间的关系。方法 经静脉注射ADM 30mg kg 2 4小时后 ,利用RT -PCR技术半定量MDR1 mRNA ;采用高效液相色谱法 (HPLC)检测内淋巴液中的ADM浓度。结果 ADM的积聚浓度与MD R1 mRNA的表达负相关 (rs=- 0 .90 1,P <0 .0 1) ,经曲线回归分析表明 ,呈二次曲线关系 (Y =182 .0 2 2 - 35 4 .79X +2 4 2 .877X2 ,Rsq =0 .815 )。结论 MDR1 基因在耳蜗外侧壁中的表达 ,可能与减少耳毒性药物在内淋巴液中的积聚 ,增强耳蜗自我保护功能有关。

Objective To study the relationship between the expression of MDR 1 gene in cochlea lateral wall and the accumulation of adriamycin in endolymph of guinea pig.Methods Twenty four white guinea pigs with red eyes were randomly chosen,and administered an intravenous injection of 30 mg/kg adriamycin or N.S.The animals were sacrificed 24 hours later,the cochlea lateral wall was then immediately removed after the endolymph was drawn by the siphon from the basal turn of cochlea. The expression of the MDR 1 mRNA in cochlea lateral wall of guinea pigs were observed by RT-PCR.The ADM concentration in endolymph was measured by high performance liquid chromatography.Results The accumulation of adriamycin in endolymph negatively correlated with the expression of MDR 1 gene in cochlea lateral wall(r s=-0.901, P <0.01).The regression analysis showed it was conical relationship (Y=182.022-354.79X+242.877X 2,Rsq=0.815).Conclusion The expression of MDR 1 gene in cochlea may reduce the accumulation of ototoxicity substance in endolymph,and have to the protective function of the blood-labyrinth barrier.