CAJ | 학술논문

以异育银鲫(Carassais auratus gibebio)为研究对象,采用组织匀浆法和高效液相色谱法,研究了双氟沙星(Difloxacin, DIF)通过异育银鲫血脑屏障情况,并比较分析了大脑和外周组织中DIF消除差异。结果显示,根据DIF 96h 半数致死剂量(2840 mg/kg b.W)给药后,第96h时异育银鲫大脑组织匀浆中DIF的含量为(10.49±0.35)μg/g；同时在临床推荐用药剂量(20 mg/kg)给药后的15个时间点(0?960h)上均能从大脑组织匀浆中检测出DIF。上述结果表明DIF能渗透通过血脑屏障而进入异育银鲫大脑组织。另外,在大脑和外周组织消除过程上,以大脑组织中的DIF消除过程最为平缓(按照20 mg/kg给药)。到试验第960h,大脑组织中DIF含量最高,为(0.392±0.007)μg/g,且大脑中的消除半衰期最长,为1157.713h。因此,异育银鲫大脑组织可作为 DIF 药物残留分析的靶组织。另根据欧盟关于食品中 DIF 最大残留限量(MRL)之规定,实验条件下DIF 休药期至少为25d。结果为研究鱼类血脑屏障作用, DIF 神经毒性及其在水产养殖上的临床应用提供了参考。
이이육은즉(Carassais auratus gibebio)위연구대상,채용조직균장법화고효액상색보법,연구료쌍불사성(Difloxacin, DIF)통과이육은즉혈뇌병장정황,병비교분석료대뇌화외주조직중DIF소제차이。결과현시,근거DIF 96h 반수치사제량(2840 mg/kg b.W)급약후,제96h시이육은즉대뇌조직균장중DIF적함량위(10.49±0.35)μg/g；동시재림상추천용약제량(20 mg/kg)급약후적15개시간점(0?960h)상균능종대뇌조직균장중검측출DIF。상술결과표명DIF능삼투통과혈뇌병장이진입이육은즉대뇌조직。령외,재대뇌화외주조직소제과정상,이대뇌조직중적DIF소제과정최위평완(안조20 mg/kg급약)。도시험제960h,대뇌조직중DIF함량최고,위(0.392±0.007)μg/g,차대뇌중적소제반쇠기최장,위1157.713h。인차,이육은즉대뇌조직가작위 DIF 약물잔류분석적파조직。령근거구맹관우식품중 DIF 최대잔류한량(MRL)지규정,실험조건하DIF 휴약기지소위25d。결과위연구어류혈뇌병장작용, DIF 신경독성급기재수산양식상적림상응용제공료삼고。
Nowadays, difloxacin (DIF) which belongs to Fluorine quinolones (FQNS), has become one of the widely used drugs. For aquatic animals, the permeability of DIF getting through blood-brain barrier has not been reported. Using Carassius auratus gibelio as the research object, the blood-brain barrier permeability of DIF and its elimination comparative study between brain and peripheral tissues were conducted with tissue homogenate and high performance liquid chromatography (HPLC) methods. The results showed that, at the 96th hour, the content of DIF in brain tissue homogenate was (10.49±0.35) μg/g following its 96 hour median lethal dose (96h LD50); and the existences of DIF in brain could be detected at the 15 time points (0?960h) after the administration with its clinical recommended dosage (20 mg/kg). The results indicated that the DIF could penetrate through the blood-brain barrier into brain of C. auratus gibe-lio. In addition, the elimination process of DIF in brain after the administration of 20 mg/kg was the gentlest one among the tissues involved in this research. The highest content of DIF in brain was (0.392±0.007)μg/g. The highest value was reached at the 960th hour. The longest T1/2βof DIF in brain was 1157.713h. The brain of C. auratus gibelio could be used as a target tissue for DIF residual analysis. Furthermore, according to the regulation of European Union (2003) about the maximum residue limits (MRL) of DIF on food, the withdrawal time of DIF should be longer than 25d under the ex-periment conditions. The results would provide references for blood-brain barrier researching in fish, and for nerve toxi-city explorations of DIF and its clinical application in aquaculture.