鞘内注射万古霉素对新西兰家兔的神经毒性研究

Neurotoxicity study on New Zealand rabbits which intrathecal injection of Vancomycin

目的：通过观察新西兰家兔鞘内注射不同剂量万古霉素后血清及脑脊液中髓磷脂碱性蛋白（myelin basic protein，MBP）的变化了解鞘内注射万古霉素的安全性。方法：建立新西兰家兔鞘内置管动物模型。按鞘内注射剂量分为低、中、高剂量三组，研究组鞘内注射万古霉素，对照组鞘内注射同量的生理盐水，每隔4小时分别抽取脑脊液及血液测定MBP含量，直至注射后24小时，绘制MBP时间曲线。结果：低中剂量组血液及脑脊液中MBP含量与对照组无明显差异，高剂量组血液及脑脊液中MBP含量高于对照组，差异有显著性。结论：常规剂量鞘内注射万古霉素用药24小时内未见明显神经毒性反应。高剂量万古霉素鞘内用药24小时内可能导致脑及脊髓受损。不适合鞘内注射。

Objective： To observe the change of myelin basic protein （MBP） in serum and cerebrospinal fluid of rabbits after different doses of intrathecal injection of vancomycin, understanding the safety of intrathecal injection of vancomycin. Methods： To establish the intrathecal catheter animal model of New Zealand rabbits. The animal model was divided into three groups, including the low, medium and high dose based on the intrathecal concentration. The study group was injected with vancomycin, and the control group was injected with normal saline. CSF and blood were collected to determine the content of MBP every 4 hours up to 24 hours after injection. The time curve of MBP was drawed. Results： There was no significant difference in the content of MBP in blood and cerebrospinal fluid between the low and middle dose group and the control group, but significant elevation was observed in the high dose group. Conclusion： There was no obvious neurotoxicity in the normal dose of intrathecal injection of vancomycin within 24 hours. High dose vancomycin intrathecal administration within 24 hours may lead to damage to the spinal cord, and is not suitable for intrathecal injection.