刘腾飞 孙晶 马荣荣 肖艳翼 朱凤娇 杨先乐 胡鲲

摘要：【目的】分析黄芪（Astragalus membranaceus）、柴胡（Bupleurum chinensis）和黄连（Coptis chinensis）3种中药对鲫鱼（Carassius auratus）体内吡喹酮代谢及CYP1A1和CYP3A活性的影响，明确中西药联合使用的相互作用机制，为健全水产品安全用药体系打下基础。【方法】试验共分8组（A0空白对照组和A1吡喹酮对照组投喂基础饵料，A2～A4组、B2～B4组分别投喂添加有黄芪、柴胡和黄连的饵料），饲喂30 d后，A1～A4组鲫鱼以10 mg/kg剂量单次经口灌服吡喹酮，并在给药后0.25、0.5、1、3、6、12、24、48和96 h于尾静脉采血，采用高效液相色谱法（HPLC）分析不同时间点血液中吡喹酮浓度；同时在给药3 h后测定A0～A4组、B2～B4组鲫鱼肝脏中的CYP1A1和CYP3A活性。【结果】A1～A4各组鲫鱼血液中吡喹酮浓度呈先升后降的变化趋势，A1、A2和A3组鲫鱼血液中吡喹酮达峰时间（Tmax）均为1 h，峰值（Cmax）分別为2.71、2.90和3.01 mg/L；A4组鲫鱼血液中吡喹酮达峰时间（Tmax）为3 h，峰值（Cmax）为2.50 mg/L。A2～A4组鲫鱼血液吡喹酮消除半衰期（t1/2β）与药时曲线下面积（AUC（0-∞））均高于A1组，而总体清除率（CL/F）较A1组明显降低；吡喹酮可显著提高鲫鱼肝脏CYP1A1和CYP3A活性（P<0.05，下同），而黄芪、柴胡和黄连对吡喹酮引起的CYP1A1和CYP3A活性升高具有显著抑制效果。【结论】黄芪、柴胡和黄连虽然能够提高吡喹酮在机体内的生物利用率，却延缓其代谢，致使吡喹酮在鲫鱼体内的残留时间延长，对食品安全造成极大威胁。因此，水产生产上中药与吡喹酮配伍使用时应当慎重。

关键词： 鲫鱼；黄芪；柴胡；黄连；吡喹酮；药代动力学；抑制

中图分类号： S965.117 文献标志码：A 文章编号：2095-1191（2016）09-1596-06

Abstract：【Objective】The present study was conducted to investigate the effects of three kinds of Chinese herbal medicine viz.， Astragalus membranaceus， Bupleurum chinensis and Coptis chinensis on praziquantel（PZQ） metabolism and CYP1A1 & CYP3A activities of Carassius auratus， in order to understand interactive mechanism of traditional Chinese herbal combined with western medicine， further lay foundation for optimize safety administration system of aquatic product. 【Method】The crucian carps were divided into 8 groups， blank control group（A0） and PZQ control group（A1） were fed on basic feed without Chinese herbal； groups A2-A4 and B2-B4 were fed on feed with A. membranaceus， B. chinensis and C. chinensis for 30 days， respectively. Then， the caudal vein blood samples were collected from groups A2-A4 at 0.25， 0.5， 1， 3， 6， 12， 24， 48 and 96 h after oral administration of 10 mg/kg PZQ， and PZQ concentrations of samples were simultaneously detected using high performance liquid chromatography（HPLC）. Meanwhile， activites of CYP1A1 and CYP3A in liver were determined at 3 h after oral administration of 10 mg/kg PZQ from groups A0-A4 and B2-B4. 【Result】PZQ concentrations of blood first increased and then decreased in groups A1-A4. The time to peak（Tmax） of PZQ in blood of C. auratus in groups A1， A2， A3 was 1 h， and PZQ peak concentrations（Cmax） was 2.71， 2.90 and 3.01 mg/L， respectively. But Tmax of PZQ in blood of C. auratus in group A4 was 3 h， and Cmax was 2.50 mg/L. In addition， the elimination half-life（t1/2β） and area under the curve（AUC（0-∞）） of groups A2-A4 were higher than control group（A1）， total clearance rates（CL/F） of groups A2-A4 were lower than that of group A1. PZQ could significantly improve CYP1A1 and CYP3A activities in liver of C. auratus（P<0.05， the same below）， however， the three kinds of Chinese herbal medicines（A. membranaceus， B. chinensis and C. chinensis） could inhibited CYP1A1 and CYP3A activities from increasing. 【Conclusion】A. membranaceus， B. chinensis and C. chinensis can improve the bioavailability of PZQ， but also greatly slow PZQ metabolism， resulting in PZQ remaining in body of C. cauratus for longer time. So， compatibility of Chinese herbal medicine and PZQ should be considered seriously in aquaculture.

Key words： Carassius auratus； Astragalus membranaceus； Bupleurum chinensis； Coptis chinensis； praziquantel（PZQ）； pharmacokinetics； inhibit

0 引言

【研究意义】中药药性温和、安全、无耐药性，西药则具有见效迅速的特点，二者合理联用可达到减毒增效、趋利避害的目的，但若使用不当，不仅会降低药效、增加药物残留，还会影响机体的健康状况，甚至危及生命安全。在水产养殖过程中，中药通常作为添加剂添加到基础饵料中，具有提高免疫、防治疾病、促进生长发育及改善水产品品质等一系列作用（史会来等，2007）；当有病害发生时，为了尽快驱除病害及降低损失，绝大部分养殖场仍然使用抗生素（西药），间接导致了中西药联合使用的现象。……