对氧磷酶1对敌敌畏毒代动力学的影响

Paraoxonase-1 Effect on Dichlorvos Toxicokinetics

目的通过研究对氧磷酶1(PON1)对有机磷药物代谢动力学影响,证明PON1是有前景的有机磷催化清除剂。方法将Wistar大鼠随机分成:染毒组(A组):腹腔注射敌敌畏(DDVP)10 mg/kg;PON1预处理组(B组):尾静脉注射纯化兔血清PON1 9 600 U/kg,30 min后腹腔注射DDVP 10 mg/kg;治疗组(C组):DDVP 10 mg/kg腹腔注射后,立即(<2 min)尾静脉注射阿托品0.05 mg/kg+解磷定120 mg/kg;联合治疗组(D组):尾静脉注射PON1 9 600 U/kg,30 min后腹腔注射DDVP 10 mg/kg,立即尾静脉注射阿托品0.05 mg/kg+解磷定120 mg/kg。于各时间点采血,液-质联用法测定血中敌敌畏含量。比较同一时间点敌敌畏浓度及各组的毒代动力学参数。结果对相同时间点DDVP浓度进行单因素方差分析,A组与C组间及B组与D组间差异无统计学意义,A组、C组与B组、D组间差异有统计学意义(P<0.05)。对4组的毒代动力学参数进行一元方差分析,曲线下面积数比较A组与C组间及B组与D组间差异无统计学意义,A组、C组与B组、D组间差异有统计学意义。平均保留时间数据4组间差异无统计学意义。峰浓度值A组和C组间差异无统计学意义,B组和D组间差异无统计学意义。A组、C组与B组、D组间差异有统计学意义(P<0.05)。结论纯化兔血清PON1可以明显改善大鼠体内胆碱酯酶抑制水平。对敌敌畏毒物代谢动力学参数影响表现为较小的曲线下面积(0→∞)及峰浓度值降低,但对平均保留时间影响不大,所以PON1可以明显降低敌敌畏入血量,降低峰浓度。

Objective To investigate the effect of paraoxonase-I （PON1） on dichlorvos toxicokinetics,to prove that it is a promising scavenger on organophosphates intoxication. Methods Wistar rats were randomly divided to 4 groups：dichlorvos administration group （A group） ：dichlorvos dissolved in corn oil was injected by intraperitaneal in a dose of 10 mg/kg. Paraoxonase-1 （PON1） pretreatment group （B group ） ： PON1 was injected in the tail vein in a dose of 9 600 U/kg before 30min of dichlorvos administration. Treatment group （ C group ） ： atropine 0.05 mg/kg and pyraloxime chloride （PAM-CI） 120 mg/kg were injected via tail vein within 2 min after dichlorvos administration. Co-treatment group （D group）：PONI was injected in the tail vein in a dose of 9 600 U/kg before 30 rain of 10 mg/kg dichlorvos administration by intraperitoneal,atropine 0.05 mg/kg and pyraloxime chloride （PAM-CI） 120 mg/kg were injected via tail vein in 2 rain after dichlorvos administration. Blood was collected, plasma dichlorvos concentration was detected by liquid chromatography-mass spectra （LC-MS） method. Dichlorvos concentration was detected,toxicokinetics parameters were calculated in a statistical moment model. Results AUC （0→∞ ） in group B was statistically different from that of group A and C （P 〈 0.05 ）, while it was not different from group D （P 〉 0.05 ） ; there was no statistical difference between group A and group C（P 〉 0.05 ）. The statistical results of Cmax were the same as AUC （0-→∞）（p 〉 0.05 ）. There were no difference of MRT among four groups （P 〉 0.05 ）. Conclusion PON1 could decrease the amount of dichlorvos that entered blood, lowed down the peak concentration,, while atropine ＋ PAM-CI did not affect metabolism of dichlorvos.