摘要
目的:观察脑梗死后SAPK/JNK及Bcl-2/Bax信号途径中关键蛋白质的变化,以探寻各种病理因素引发神经元凋亡的分子机制。方法:SD大鼠36只随机分为脑梗死组和假手术组。光化学法制作大脑皮层局灶缺血梗死模型,称作光血栓皮层损伤(PCI)。7 d后取梗死灶同侧的大脑皮层行电镜检查,以Western blotting分析p-JNK1、p-JNK2、p-c-Jun、p-ATF-2、total JNK1、total JNK2、Bcl-2和Bax等关键蛋白的水平变化。结果:光化学法可以成功复制大脑皮层局灶缺血梗死模型。在PCI后7 d,脑梗死组可见到神经元细胞凋亡和广泛的细胞器病变,p-JNK-1、p-JNK-2以及其下游的p-c-Jun、p-ATF-2的水平较假手术组显著升高,Bcl-2/Bax的比值显著降低(P<0.05)。结论:脑梗死发生后在较长的一段时间内都存在着以神经元凋亡为表现形式的迟发性神经细胞死亡,而这一过程可能与缺血缺氧性损伤激活了SAPK/JNK信号通路,及调节凋亡相关蛋白(如Bcl-2/Bax)等机制有关。
AIM： To investigate the molecular mechanism of neuronal apoptosis by observing the changes of key proteins in SAPK/JNK and Bcl -2/Bax signal pathways after brain infarction. METHODS： The cortical infarction was induced by photochemistry, namely photothrombotic cortical injury （PCI）. Thirtysix Sprague- Dawley rats were randomly divided into 2 groups： PCI group and sham -operated group. The ipsilesional cortex was harvested for histomorphometry and transmission electron microscopy 7 days after PCI. Some key proteins including p - JNK1, p - JNK2, p - c - Jun, p - ATF - 2, total JNK1, total JNK2, Bcl - 2 and Bax were detected by Western blotting analysis. RESULTS： The cortical infarction in rats was successfully induced by photochemistry. The apoptosis of neurons in cortex was more obvious in PCI group than that in sham - operated group 7 days after PCI. The levels of p - JNK1, p - JNK2, p - c - Jun and p - ATF - 2 in PCI group were significantly higher than those in sham - operated group, whereas the ratio of Bcl - 2/Bax was significantly lower（P 〈 0. 05）. CONCLUSION： Apoptosis is a major contributor to neuronal loss induced by cerebral hypoxia - ischemia for a long period after cortical infarction. The process is related to some apoptotic proteins such as Bcl - 2/ Bax and the SAPK/JNK signal pathways activated by ischemic injury.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2011年第8期1552-1556,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81071030)
广东省科技计划资助项目(No.2010B031600089)
中大青年教师培育资助项目(No.09ykpy31)
