咪达唑仑直肠给药的部分药代学与其抗大鼠皮层惊厥阈值及海马病理改变

An observation of per-rectal midazolam in relation to its pharmacokinetics in human as well as anticonvulsive effect and hippocampal neuroprotection in rats

目的探讨咪达唑仑直肠给药短时间的吸收情况和抗惊厥效果,以及对海马神经元的保护作用。方法①咪达唑仑直肠给药后,采用高效液相色谱法测定人血清中的药物浓度,观察其吸收情况;②用直接电刺激大鼠皮层惊厥模型作为观察对象,动态观察咪达唑仑直肠给药30min内,11个时间段的药效和时效的变化,实验结束后与对照组比较其海马神经元的组织学变化。结果①咪达唑仑直肠给药吸收迅速,用药安全;②咪达唑仑、地西泮均能显著提高模型大鼠的惊厥阈值(P<0.05),但前者抗惊厥效应更强,能更快发挥作用;③咪达唑仑组的海马神经细胞损害较轻。结论咪达唑仑直肠给药后,几分钟内即可产生有效的抗惊厥作用,且对海马神经元产生保护作用,其作用强于地西泮。

Objective To study the acute absorption, anticonvulsive effect and hippocampal neuroprotection of per-rectal midazolam. Methods ① High performance liquid chromatography was used to examine the serem concentration and absorption time of per-rectal midazolam in human;② Using rat models of convulsion induced by direct cortical stimulation, the anficonvulsive effect and time-effect profile of per-rectal midazolam at 11 time-spots within the first 30 minutes following medication were observed. At the end of experiment, pathology of rat hippecampus was examined and compared with controls. Results ①Per-rectal midazolam was safe with quick absorption. ②While both of midazolam and diazepam elevated the convulsion threshold in rats （ P〈0.05 ）, the effect of former was more quickly and effectively. ③ The neuronal injury appeared milder in the group treated with per-rectal midazolam. Conclusion Per-rectal midazolam showed anficonvulsive effects within minutes after administration and provided stronger hippocampal neuroprotection as compared with diazepam.