双氟沙星对异育银鲫血脑屏障渗透性及消除规律

BLOOD-BRAIN BARRIER PERMEABILITY OF DIF AND ITS ELIMINATION COMPARATIVE STUDY BETWEEN BRAIN AND PERIPHERAL TISSUES IN CARASSIUS AURATUS GIBELIO

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。

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.