糖尿病导致加替沙星在小鼠中枢神经系统的毒性增加  

Increase of gatifloxacin toxicity in central nervous system of diabetic mice

作　　者：朱晓琳[1] 李杨[1] 李峰[1] 庄毅超[1] 钮晓淑[1] 谢林[1] 刘晓东[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室,南京210009

出　　处：《中国药科大学学报》2009年第1期80-83,共4页Journal of China Pharmaceutical University

基　　金：国家基础科学人才培养基金资助项目(No.J0630858);国家自然科学基金资助项目(No.30672499)~~

摘　　要：目的:研究加替沙星(GFLX)在糖尿病小鼠中枢神经系统毒性和脑内的分布变化。方法:给链脲佐菌素3周后,糖尿病小鼠尾静脉注射GFLX,以癫痫发作为指标,观察GFLX在中枢神经系统的毒性与GFLX是否增加阈下剂量(25mg/kg)戊四唑诱发癫痫发作。同时测定GFLX在小鼠血中与脑中浓度。结果:静脉注射200 mg/kg GFLX可以诱发小鼠癫痫发作,糖尿病小鼠发作频率和强度明显大于正常小鼠。合用100 mg/kg GFLX,能诱发阈下剂量戊四唑引起的糖尿病小鼠癫痫发作,但不能诱发正常小鼠癫痫发作。药动学结果显示GFLX在糖尿病小鼠血中和脑内浓度均低于正常小鼠。结论:GFLX在糖尿病小鼠中枢神经系统毒性增加,诱发癫痫发作,该作用不是脑内药物浓度增加所致。Aim： To investigate whether diabetes mellitus would affect gatifloxacin （GFLX） toxicity in central nervous system of diabetic mice and modulate the distribution of GFLX in the brain. Methods： Three-week diabetic mice were induced by ip administration of 190 mg/kg streptozotocin. Epilepsy occurrences, used as a biomarker, were observed after iv injection of 200 mg/kg of GFLX or 100 mg/kg of GFLX plus subthreshold dose （ 25 mg/kg） of pentylenetetrazole（PTZ）. Meanwhile, GFLX concentrations in brain and plasma were measured after iv administration of GFLX （ 80 mg/kg）. Results： The incidence frequence and intensity of GFLX-induced epilepsy in diabetic mice were higher than those in normal mice after iv administration of 200 mg/kg of GFLX. Adminsitration of GFLX （ 100 mg/kg） resulted in epilepsy occurrence induced subthreshold dose of PTZ in diabetic mice, but no change was found in normal mice. Further study demonstrated that there were lower concentrations of GFLX in brain and plasma in diabetic mice than in normal mice. Conclusion： Diabetes mellitus resuited in the increased GFLX toxicity in the central nervous system. The enhancement in GFLX-induced epilepsy occurrence in diabetic mice may not result from the increase of GFLX level in brain.

关 键 词：加替沙星 糖尿病 血脑屏障 癫痫 

分 类 号：R587.1[医药卫生—内分泌] R96[医药卫生—内科学]