内源性组胺对大鼠戊四唑点燃癫痫诱发记忆障碍的作用

Effects of endogenous histamine on memory impairment induced by pentylenetetrazole-kindled epilepsy in rats

目的:研究大鼠戊四唑点燃癫痫诱发记忆障碍的发病机制,并探讨内源性组胺对此类记忆障碍的作用。方法:大鼠隔日腹腔注射亚惊厥剂量(35 m g/kg)的戊四唑,直至完全点燃。采用穿梭箱被动回避试验测定大鼠的记忆能力。化学荧光法测定脑内组胺含量。大鼠脑病理切片采用HE染色,在光学显微镜下计数海马完整神经元。结果:大鼠戊四唑点燃后记忆能力明显下降,表现为穿梭箱内被动回避反应潜时缩短,而腹腔内注射组胺前体物质组氨酸则阻断了被动回避反应潜时的缩短。戊四唑点燃后大鼠海马、丘脑和下丘脑组胺含量明显下降,同时点燃使海马CA 1区和CA 3区完整神经元数目分别减少至对照组的72.7%和78.9%。结论:戊四唑点燃癫痫可导致大鼠记忆能力下降,可能与癫痫造成的组胺能神经活性降低和海马神经元丢失有关。

Objective： To investigate the mechanisms of memory impairment induced by pentylenetetrazole （PTZ）-kindled epilepsy in rats and the effects of endogenous histamine. Methods. Rats were injected i. p with a subconvulsive dose of PTZ every 48 h until fully kindled. Memory was tested by shuttle box with passive avoidance. Brain histamine was measured spectrofluorometrically. Neurons of hippocampus were investigated with HE stain. Results： PTZ - kindled epilepsy caused memory impairment in rats, i. e. latency of passive avoidance was shortened in shuttle box. Pretreatment of histidine, the precursor of histamine, showed an ameliorating effect on memory impairment induced by epilepsy. Decreased histamine contents in the hippocampus, thalamus and hypothalamus were observed after fully kindled in rat. In addition,intact neurons of the CA1 and CA3 regions in hippocampus decreased to 72.7% and 78.9% compared with those in control group. Conclusion： PTZ-kindled epilepsy causes memory impairment, and it might be due to a decrease of brain histamine and loss of hippocampal neurons induced by epilepsy.