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应用北京医科大学培育的听源性癫痫易感大鼠P77PMC,以癫痫不易感大鼠Wistar为对照,系统研究了NMDA受体亚单位Ⅰ(NR1)与白细胞介素1(IL1)在癫痫发生发展中的作用及相互关系。实验在整体、脑片、神经细胞培养及分子水平进行。所得较有意义的结果如下:(1)在听源性惊厥易感大鼠P77PMC整个发育过程中脑内NR1mRNA的表达,以及成年鼠脑内NMDA受体活性(MK801结合)都高于对照组Wistar大鼠。惊厥后P77PMC脑内NR1mRNA的表达呈时间依赖性增加,惊厥后24h比惊厥前增加111%~202%;NR1反义寡核苷酸脑室注射(每μl10μg)可显著减轻P77PMC大鼠惊厥程度,并可对谷氨酸引起的体外神经细胞的损伤有保护作用,抑制谷氨酸导致的神经毒性作用。由此证实NR1参与惊厥的发生发展,并与P77PMC大鼠的遗传性癫痫易感性关系密切。(2)在神经细胞培养中IL1β可明显剂量依赖性地(1~25U·ml1)提高NR1mRNA的表达,白细胞介素1受体拮抗剂(IL1ra)可阻断此效应;IL1β可剂量依赖性地提高NR1受体活性,因此提示IL1具有兴奋性神经调质的作用,其作?
Application of Beijing Medical University to cultivate the auditory epilepsy susceptible rat P77PMC to epilepsy in rats Wistar as a control, the system of NMDA receptor subunit Ⅰ (NR 1) and interleukin 1 (IL 1 ) In the development of epilepsy and their relationship. Experiment in the whole, brain slices, nerve cell culture and molecular level. The more meaningful results obtained are as follows: (1) In the whole process of development of auditory convulsion-prone P77PMC, the expression of NR-1 mRNA in the brain and the NMDA receptor activity (MK-801 binding) in adult rat brain were both high Wistar rats in control group. The expression of NR-1 mRNA in the brain of P77PMC increased in a time-dependent manner after convulsion, and increased by 111% ~ 202% at 24h after convulsion. Compared with preconditioning, NR1 antisense oligonucleotide injected intracerebroventricularly (10μg / μl) significantly reduced P77PMC rats Convulsions, and glutamate-induced damage to nerve cells in vitro protective effect of glutamate-induced neurotoxicity. Thus confirmed that NR 1 involved in the occurrence and development of convulsions and P77PMC rats with genetic epilepsy susceptibility are closely related. (2) In the neural cell culture IL 1β significantly increased dose-dependently (1 ~ 25U · ml 1) NR 1mRNA expression, interleukin 1 receptor antagonist (IL 1ra) can be blocked This effect; IL 1β dose-dependent increase in NR 1 receptor activity, suggesting that IL 1 excitatory neuromodulation effect, which?