缺血再灌注后皮层神经元内蛋白酶体活性变化与延迟性神经元死亡的关系  

Study on the activities' alteration of the proteasome in neurons of cortex and its relation with delayed neuron death after reperfusion following ischemia

作　　者：葛鹏飞[1] 罗毅男[1] 付双林[1] 陈大玮[1] 王海峰[1] 于天浩[1] 刘守越[1] 

机构地区：[1]吉林大学第一医院神经外科,长春130021

出　　处：《中华医学杂志》2007年第9期637-639,共3页National Medical Journal of China

摘　　要：目的探讨缺血再灌注后大鼠皮层神经元内蛋白酶体活性改变与神经元延迟性死亡的关系。方法采用20 min 全脑缺血大鼠模型。将50只 Wistar 大鼠按照再灌注时间分为5组:假手术组、0.5 h 恢复组、4 h 恢复组、24 h 恢复组及72 h 恢复组,每组10只大鼠。以 Suc-llvy-amc 为底物测定蛋白酶体的活性;采用 HE 染色在光镜下观察缺血再灌注后神经元的死亡。应用免疫组织化学法结合激光扫描共聚焦显微镜观察缺血再灌注后蛋白酶体在细胞内的分布。结果假手术组蛋白酶体活性[吸光度(A)值]为54 602±1602,缺血再灌注0.5 h 后蛋白酶体活性为42 036±1465(与假于术组比较,P<0.01),虽然4 h 后其活性一过性恢复到47 536±2532(P<0.05),但24 h 后则下降为45 450±649(P<0.01),再灌注后72 h 其活性为43 108±995(P<0.01)。HE 染色显示,缺血冉灌注72 h 后,可见皮层神经元部分死亡。激光共聚焦扫描显微镜显示缺血再灌注24 h 后,皮层神经元的胞核与胞质内的蛋白酶体都有减少,72 h 后死亡神经元胞核内的蛋白酶体几乎全部消失,周围的胞质内只有少量蛋白酶体。结论全腑缺血再灌注后,蛋白酶体活性下降是导致神经元延迟性死亡的一个重要因素。Objective To investigate the activities＇ alteration of the proteasome in neurons of cortex and its relation with delayed neuron death after reperfusion following ischemia. Methods 20 minutes transient global ischemia rat model was used. Following different reperfusion period, all the 50 rats were divided into 5 groups, sham-operation group, 0.5 hour recovery group, 4hours recovery group, 24 hours recovery group and 72 hours recovery group, 10 rats each group. Suc-llvy-amc was used as substrate for measuring proteasome＇s activities. Delayed neuron death after reperfusion following ischemia was observed under hght microscope by HE staining. Proteasome＇s distribution was observed under laser scanning confocal microscope after immuno-histo- chemical staining. Results The proteasome activity of sham group was 54 602 ± 1602, and that of 0.5 h reperfusion following ischemia was 42 036 ± 1465 （ compared with sham group, P 〈 0.01 ）. Although the proteasome activity temporarily recovered to 47 536 ± 2532 （ P 〈 0.05 ） after 4 h reperfusion, it still decreased to 45 450 ± 649 （ P 〈 0.01 ） after 24 h reperfusion, and to 43 108 ± 995 （P 〈 0.01 ） after 72 h reperfusion. HE staining showed that parts of neurons in the cortex died after 72 hours reperfusion. Under laser scanning microscope, we could observe that after 24 hours reperfusion, proteasome in both nucleus and cytoplasma significantly decreased; after 72 hours reperfusion, proteasome almost disappeared totally in nucleus and only a small part of proteasome still existed in cytoplasm. Conclusions Decreasing of the proteasome＇s activities is an important factor for delayed neuron death after reperfusion following ischemia.

关 键 词：缺血再灌注 皮层神经元 蛋白酶体 延迟性神经元死亡 

分 类 号：R363[医药卫生—病理学]