内源性组胺参与吗啡调节戊四唑癫痫易感性过程

Involvement of endogenous histamine in modulatory effect of morphine on seizure susceptibility in mice

目的:研究吗啡对戊四唑(PTZ)癫痫易感性的调节作用,同时探讨内源性组胺在该调节过程中的作用。方法:在组氨酸脱羧酶(组胺合成关键酶)基因敲除及其相应野生型小鼠皮下注射不同剂量的吗啡,1h后以0.3ml/min的恒定速度尾静脉注射1.5%的化学致痫剂戊四唑,观察达到肌阵挛及全身性阵挛发作的阈值。结果:吗啡可以剂量依赖性地降低野生型小鼠达到肌阵挛及全身性阵挛发作的阈值,基因敲除型小鼠注射10mg/kg的吗啡后,达到肌阵挛发作的阈值从生理盐水组的(38.6±2.9)mg/kg降低到(32.5±0.7)mg/kg,具有显著性差异,而达到全身性阵挛发作的阈值从生理盐水组的(51.8±2.1)mg/kg降低到(47.6±1.2)mg/kg,没有统计学差异。另外,基因敲除鼠达到肌阵挛发作阈值的降低幅度(15.8±1.4)%及全身性阵挛发作阈值的降低幅度(8.3±0.9)%,都比野生型小鼠明显减少,分别为(26.1±2.5)%和(20.8±2.4)%。结论:吗啡可以降低戊四唑癫痫发作的阈值,从而增加癫痫的易感性,而内源性组胺参与了该过程。

Objective： To investigate the modulatory effects of morphine on the susceptibility to pentylenetetrazole-induced seizures ,and the involvement of endogenous histamine in this process. Methods： Both the wild-type （WT） mice and histidine decarboxylase （a key enzyme for histamine biosynthesis） deficient （HDC-KO） mice were subcutaneously injected with different doses of morphine,and 1 hour later the pentylenetetrazole solution （1.5%） was infused into the tail vein at a constant rate of 0. 3 ml/min. The minimal dose of pentylenetetrazole （mg/kg） needed to induce myoclonic jerks and clonus convulsion was recorded as the thresholds of seizures. Results： In WT mice,morphine dose-dependently decreased the thresholds of both myoclonic jerks and clonus convulsion. In HDC-KO mice, morphine at 10 mg/kg only significantly decreased the threshold of myoclonic jerks from （38. 6±2. 9）mg/kg to （32. 5±0. 7）mg/kg,but had no significant effect on the threshold of clonus convulsion [from （51.8±2.1）mg/kg to （47.6± 1.2） mg/kg]. In addition,the value of decreased myoclonic jerks （15.8±1.4）% and clonus convulsion （8.3±0. 9）% thresholds were much lower in HDC-KO mice than in WT mice [（26.1±2. 5）% and （20. 8 ±2.4）%, respectively]. Conclusion： Morphine can decrease the thresholds of pentylenetetrazole in induction of seizure,and the endogenous histamine may be involved in this process.