【摘要】 目的:研究和阐明中枢组胺对戊四唑(PTZ诱发大鼠点燃癫痫的作用机制.方法:隔日腹腔内注射亚惊厥剂量的PTZ 35 mg/kg诱发化学点燃癫痫,直至癫痫发作级别为4—5级.观察每次PTZ注射后30分钟内大鼠的行为变化.结果:在癫痫形成过程中,腹腔内注射组氨酸（200,500mg/kg）,一种组胺的前体,剂量依赖性地延缓出现肌性痉挛和阵挛性癫痫全身性发作的反应潜时和抑制癫痫发作的级别.在癫痫模型形成后点燃激发过程中,组氨酸（500,1000mg/kg）和组胺H₃受体阻断剂4-[4′-（环己氨基硫代甲酰基哌啶）]-4H-咪唑（10,20μg）也分别表现出了明显的抗癫痫作用（2.6±0.4,2.2±0.3）,（2.8±0.6,2.1±0.5）.组氨酸的作用可被4-[4′-（环已氨基硫代甲酰基哌啶）]-4H-咪唑（5μg）显著性增强,却被选择性组氨酸脱羧酶抑制剂α-氟甲基组胺酸（20μg）和H₁受体拮抗剂美吡拉敏（2,5mg/kg）剂量依赖性、显著性地抑制.另外,H₂受体拮抗剂卓兰替丁即使在10mg/kg剂量下也无明显的对抗作用.结论:内源性组胺在对抗阵挛性癫痫全身性发作中起到了较重要的作用,其作用主要与突触前膜H₃受体与突触后膜H₁受体相关.更多还原

【Abstract】 AIM: The effect of histidine on pentylenetetrazole-induced seizures was investigated in rats. METHODS: Chemical kindling was elicited by repeated ip injection a subconvulsant dose of pentylenetetrazole (35 mg/kg) once every 48 h until the occurrence of seizure stages 4 -5, and seizure activity of kindling was recorded for 30 min. RESULTS: In the kindling development process, ip injection of histidine (200, 500 mg/kg), a precursor of histamine, prolonged latency for the onset of myoclonic jerks and the clonic generalized seizure, and inhibited seizure stage in a dose-dependent manner. In the kindling challenge process, histidine (500, 1000 mg/ kg) and H3 antagonist thioperamide (10, 20μg) also showed a significant anticonvulsant effect. The inhibitory action of histidine was enhanced significantly by thioperamide (5μg), however, was antagonized by both α-fluoromethylhistidine ( 20μg ), a selective histidine decarboxylase inhibitor and H1 antagonist pyrilamine (2, 5 mg/kg), dose-dependently and significantly. In addition, H2 antagonist zolantidine appeared no appreciable effect, even at a dose of 10 mg/kg. CONCLUSION: These results indicated that brain endogenous histamine may play certain important role in protect against generalized clonic seizures, its action may via presynaptic H3-receptors and postsynaptic Hj-receptors.更多还原