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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H_3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H_1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,H_2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H_3受体与突触后膜H_1受体相关.
Objective: To study and clarify the mechanism of central histamine on pentylenetetrazole (PTZ) -induced epilepsy in rats.Methods: Every other day, intraperitoneal injection of sub-convulsive dose of PTZ 35 mg / kg induces epilepsy to ignite epilepsy until the level of seizure is 4- Level 5. The behavioral changes in rats were observed within 30 minutes after each PTZ injection.Results: Intraperitoneal injection of histidine (200, 500 mg / kg), a histamine precursor, in a dose-dependent manner during epileptogenesis Delayed onset of response and suppression of seizures in patients with muscle spasm and clonic epilepsy.His histamine (500, 1000 mg / kg) and histamine H_3 were stimulated during the firing challenge after the formation of the epilepsy model The blocker 4 - [4 ’- (cyclohexylthiocarbamylpiperidine)] - 4H-imidazole (10, 20 μg) also showed significant antiepileptic effects (2.6 ± 0.4, 2.2 ± 0.3) , (2.8 ± 0.6, 2.1 ± 0.5). The effect of histidine was significantly enhanced by 4- [4 ’- (cyclohexamidothiocarbamylpiperidine)] - 4H-imidazole Histone decarboxylase inhibitor a-fluoromethylhistidine (20μg) and H_1 receptor antagonist mepyramine (2,5mg / kg) dose-dependently and significantly inhibited.In addition, H_2 receptor Antagonist There was no significant antagonism of loclittine even at the dose of 10 mg / kg.Conclusion: Endogenous histamine plays a more important role in generalized seizures of clonic seizures and its role is mainly related to presynaptic membrane H_3 receptor and postsynaptic membrane H_1 receptor related.