结核性脑膜炎对莫昔沙星透过血脑屏障的影响研究

目的:以莫昔沙星为模型药物探讨结核性脑膜炎对血脑屏障通透性的影响。方法:21只小鼠尾静脉注射结核分枝杆菌菌悬液14d建立结核性脑膜炎模型;于造模成功后第2天取健康、模型小鼠灌胃给予莫昔沙星(100mg·kg-1),连续给药5d,每日1次,考察末次给药后24h内小鼠血浆和脑组织中血药浓度及药动学参数;取造模后小鼠按模型组(0.5%羧甲基纤维素钠)、治疗组(莫昔沙星,100mg·kg-1)、阳性对照组(利福平,20mg·kg-1)分别灌胃给予相应药物,每日1次,给药5d停2d,连续给药56d,考察第57天小鼠脑组织中活菌数量。结果:与健康小鼠比较,模型小鼠脑组织中莫昔沙星AUC0～24(hP<0.05)、Cmax、t1/2增加,血浆中无明显变化;与模型组比较,治疗组、阳性对照组小鼠脑组织中活菌数明显减少(P<0.05)。结论:在结核性脑膜炎存在情况下,莫昔沙星透过血脑屏障的量增加,对结核性脑膜炎模型小鼠有杀菌作用,作用与利福平相当。

Effect of Tubercular Meningitis on the Permeability of Moxifloxacin through Blood-brain Barrier

OBJECTIVE： To research the influence of tubercular meningitis on the permeability of blood-brain barrier （BBB） using moxifloxacin （Mfx） as model. METHODS： 21 mice were injected with tuberculosis mycobacteria suspension via tail vein for 14 days to induce tuberculosis meningitis model. 2 days after modeling succeeded, healthy mice and model mice were given Mfx （100 mg·kg^-1） once a day for 5 days. The concentrations and pharmacokinetic parameters of Mfx in plasma and cerebral tissue of mice within 24 h after the last administration were determined. After modeling, mice were given 0.5% sodium carboxymethylcellulose （model group）, Mfx 100 mg·kg^-1 （treatment group） and rifampin 20 mg·kg^-1 （positive control group） via i.g. gtt once a day respectively. Mice didn’t taken medicine for 2 days after 5 days of medication. Medication duration lasted for 56 days. The number of viable bacterium in cerebral tissue of mice was measured on the 57th day. RESULTS： Compared with healthy mice, AUC0～24 h （P0.05）, Cmax and t1/2 in cerebral tissue of model mice were increased while these parameters in plasma had no significant change. Compared with model group, the number of viable bacterium in cerebral tissue of mice in treatment group and positive control group were decreased significantly （P0.05）. CONCLUSIONS： Tubercular meningitis can promote Mfx penetrating across BBB. Mfx can be used for the therapy of tubercular meningitis as rifampin.