【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。更多还原

【Abstract】 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 time- points. Results: In MT group the level of caspase-3 cleaved fragments was down regulated, associated with up- regulation 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.更多还原