异育银鲫体内阿维菌素血脑屏障渗透性及组织残留

Blood-brain barrier permeability and residual tissue characteristics of Avermectin(AVM) in Carassius auratus gibelio

采用脑组织匀浆法和高效液相色谱法(HPLC),检测异育银鲫(Carassius auratus gibelio)体内不同浓度下阿维菌素(Avermectin,AVM)血脑屏障渗透性及其组织残留情况。结果显示,AVM在其3个半数致死浓度(24 h LC50:0.127 mg/L、48 h LC50:0.071 mg/L、96 h LC50:0.039 mg/L)及其安全用药浓度(0.003 9 mg/L)下,均能从异育银鲫脑组织中检测出AVM;其中24 h LC50浓度下脑中AVM含量最高,为(0.292±0.005)μg/g;并且各半数致死浓度之间脑中AVM含量差异均极显著(P<0.05)。结果表明,不同浓度条件下AVM均能渗透通过血脑屏障进入异育银鲫脑组织,其含量与AVM用药浓度呈正相关。另外,在安全用药浓度(0.003 9 mg/L)条件下,AVM在各组织中的浓度时间数据经DAS 3.0药物代谢动力学软件拟合后发现均符合非房室模型,其主要药代动力学参数大小关系表现为:(1)达峰时间(Tmax):肌肉<脑<肝<肾;(2)峰浓度(Cmax):肝>肾>肌肉>脑;(3)末端消除半衰期(T1/2Z):肝>脑>肾>肌肉;(4)药时曲线下面积(AUC):肝>肾>脑>肌肉。本研究结果可为研究鱼类血脑屏障、AVM神经毒性及其在水产养殖上的应用提供参考。

Using tissue homogenate and high performance liquid chromatography（HPLC） methods, the blood-brain barrier permeability and residual tissue characteristics in Carassius auratus gibelio were examined under different Avermectin （AVM） concentrations. AVM was detected in the C. auratus gibelio brain under the median lethal concentrations （LC50= 0.127 mg/L, 0.071 mg/L, and 0.039 mg/L）） at 24 h, 48 h, and 96 h, respectively and the safety concentration （SC： 0.003 9 mg/L）. Significant differences in the brain AVM contents among the three median lethal concentrations were observed（P〈0.05）. The brain AVM content was highest at 24 h LC50 [（0.292±0.005） μg/g]. The above results show that AVM can penetrate the blood-brain barrier into the C. auratus gibelio brain under different concentrations. Furthermore, the brain AVM contents were positively correlated with initial drug concentration. In addition, the AVM concentration-time data in the brain, liver, kidney, and muscle were all in line with the non-compartmental method in the DAS 3.0 pharmacokinetics software under the safe concentration （0.0039 mg/L）. The main pharmacokinetic parameters were as follows： （1） Tmax： muscle〈brain〈 liver〈kidney;（2） Cmax： liver〉kidney〉muscle〉brain; （3） T1/2z： liver〉brain〉kidney〉muscle; （4） AUC： liver〉kidney〉 brain〉muscles. The results of this paper provide references for future fish blood-brain barrier research, and AVM nerve toxicity mechanism investigations and its application in aquaculture.