摘要
目的:观察癫发作后不同时间海马组织凋亡相关蛋白表达水平的变化,探讨米诺环素(MT)减轻癫所致的海马神经元损伤的机制。方法:杏仁核立体定向注射红藻氨酸(KA)建立大鼠癫模型,随机分为治疗(MT)组和非治疗(KA)组,以杏仁核注射生理盐水为空白对照(SC)组。用免疫印迹法检测caspase-3裂解片段及Bcl-2和Bcl-xl表达水平的变化。结果:与KA组相比,MT组caspase-3裂解水平明显降低(P<0.05)并接近SC组;Bcl-2在癫发作终止后2h开始上调,24h达高峰并持续到72h。Bcl-xl上调不明显。结论:米诺环素能减少caspase-3的裂解,抑制线粒体凋亡通路激活,从而减轻癫发作对神经元的损伤。这一作用与抗凋亡因子Bcl-2的上调有关,提示Bcl-2可能是癫潜在的治疗靶点。
Aim： To observe level changes of apoptotic proteins in hippocampus of rats at various time-points after seizure, and to explore the protective effects of minocycline on neuronal injuries induced by epilepsy. Methods： The model of seizure rats was established by injecting kainic acid （KA） to intra-amygdaloid by stereotactic apparatus. Then the rats were randomly divided into minocycline-treated group （MT group） and non-minocycline treated group （KA group）. Rats in control group （SC group） accepted intra-amygdaloid injection of saline instead of KA. Bcl-2, Bcl-xl and caspase-3 （33 000）/caspase-3 cleaved product （17 000） in hippocampus were detected at various timepoints. Results： In MT group the level of caspase-3 cleaved fragments was down regulated, associated with upregulation of anti-apoptosis protein Bcl-2. The up-regulation of Bcl-2 was observed as early as 2 hours after seizures ceased, peak level reached at 24 hours, and lasted to 72 hours. Conversely, Bcl-xl was not up regulated obviously; difference can only be observed between MT group and normal control group at 48h after seizure. Conclusion： Minocycline can reduce cleavage of caspase-3 and inhibit activation of mitochondria-dependent apoptotic signaling pathway after acute injury induced by seizure. This effect is contributed to up-regulation of Bcl-2. Anti-apoptosis protein Bcl-2 is possibly therapeutic target in treatment of brain injury associated with seizures.
出处
《中国临床神经科学》
2006年第4期362-367,共6页
Chinese Journal of Clinical Neurosciences
关键词
癫痫
海马
米诺环素
凋亡
epilepsy
hippocampus
minocycline
apoptosis
