脑缺血大鼠缺血同侧海马齿状回突触可塑性的变化

Change in the synaptic plasticity of ischemic hippocampal dentate gyrus in rats with focal cerebral ischemia

目的:观察缺血性脑损伤对缺血同侧海马齿状回突触可塑性的影响。方法:实验于2005-06/2005-08在中国科技大学生命科学院神经毒理实验室完成。24只雄性Wistar大鼠分为假手术2周组和缺血2周组两组,采用热凝闭大鼠大脑中动脉致局灶性脑缺血模型,待大鼠苏醒后(术后3h)及2周后分别观察大鼠行为表现并进行神经功能缺损评分。模型制作14d后进行海马齿状回区反应波形测定和实验参数测定,观察缺血同侧海马齿状回区的I/O曲线,缺血同侧海马齿状回区长时程增强,缺血同侧海马齿状回区长时程抑制。结果:2组各12只大鼠均进入结果分析。假手术组有9只大鼠引出反应波形,缺血组有8只大鼠引出反应波形,排除过高或过低数值,每组有6只大鼠进入数据分析。①缺血2周后缺血同侧海马齿状回兴奋性突触后电位的I/O曲线幅度显著降低穴F=43.95,P<0.05雪,群峰电位的I/O曲线幅度也显著降低穴F=4.58,P<0.05雪。②兴奋性突触后电位的长时程增强幅度在假手术组为(109.0±3.8)%,缺血2周后升高为(114.0±1.9)%穴F=13.79,P<0.05雪。群峰电位的长时程增强幅度在假手术组为穴201±13雪%,而在缺血组群峰电位的长时程增强幅度明显降低为穴179.0±13雪%穴F=4.56,P<0.05雪。③兴奋性突触后电位的长时程抑制幅度在假手术组为(98.7±3.4)%,缺血2周后明显降低为(89.0±3.5)%穴F=18.95,P<0.05雪。群峰电位的长时程抑制幅度在假手术组为(84.7±5.3)%,而在缺血组群峰电位的长时程抑制幅度为(85.6±3.9)%,与假手术组无明显区别穴F=0.63,P>0.05雪。结论:脑缺血降低了海马齿状回区基本的突触传递,同时降低单脉冲刺激海马穿通纤维引起的齿状回颗粒细胞的共同发放幅度;缺血损伤了海马齿状回区群峰电位的长时程增强诱导,而对兴奋性突触后电位的长时程增强诱导有促进作用;缺血损伤了海马齿状回区兴奋性突触后电位的长时程抑制诱导,而对群峰电位的长时程抑制诱导没有明显影响。

AIM： To observe the effect of focal cerebral ischemia on the synaptic plasticity of hippocampus dentate gyrus in homonymy. METHODS： The experiment was conducted in the Laboratory of Nervous Toxicology of College of Life in the University of Science and Technology of China from June to August 2005. A total of 24 male adult Wistar rats were divided into 2 groups： 2-week sham-operation group and 2-week ischemic group. Models of focal cerebral ischemia were established by heat coagulating occlusion of the middle cerebral artery. Performances of rats were observed after analepsia （3 hours after operation） and 2 weeks later respectively to evaluate the score of neurological impairment. At 14 days after the modeling, the waveform of hippocampus dentate gyrus region and the experimental parameters were detected, and the I/O curve of hippocampus dentate gyrus region of ischemic side was observed, and long-term potentiation presented in the hippocampus dentate gyrus region of ischemic side, moreover, long-term depression （LTD） presented in the hippocampus dentate gyrus region of ischemic side. RESULTS： A total of 2 groups including 12 rats were involved in the analysis of results. Nine rats in the sham-operation group got waveform and 8 rats in the ischemic group had reaction, those with over-high or over-low value were excluded, and there were 6 rats in each group entered the data analysis. ①The slope of I/O curve of excitatory post-synaptic potential （EPSP） in hippocampus dentate gyrus region of ischemic side at 2 weeks after ischemia was significantly depressed （F=43.95, P 〈 0.05）; ②The amplitude of long-term potentiation of EPSP in the sham-operation group was （109.0±3.8）%, which increased to （114.0±1.9） % （F=13.79,P 〈 0.05） at 2 weeks after ischemia. The long-term potentiation of population spike in the sham-operation group was （201±13）%, whereas that in the ischemic group obviously decreased to （179.0±13）% （F=4.56,P 〈 0.05）; ③The amplitude of LTD of EPAP in the sham-operation group was （98.7±3.4） %, which remarkably decreased to （89.0±3.5）% （F=18.95, P 〈 0.05） at 2 weeks after ischemia, The amplitude of LTD of population spike in the sham-operation group was （84.7±5.3）%, whereas that in the ischemic group was （85.6±3.9）% ,which was not obviously different from that in the sham-operation group （F=0.63 ,P 〉 0.05）. CONCLUSION： Cerebral ischemia reduces the basic synapic transmission of hippocampus dentate gyrus region, meanwhile, reduces the synchronous firing amplitude of dentate granule cells evoked by single-shock stimulated bippocampus perforating fibrbs; Ischemia impairs the induction of long-term potentiation of population spike in the hippocampus dentate gyrus region, whereas has a promotive effect on the induction of long-term potentiation of EPSP; It injures the induction of LTD of EPSP, but has no obvious effect on the induction of LTD of population.