载脂蛋白E拟肽COG1410对蛛网膜下腔出血后自噬和凋亡的影响

发布时间：2018-08-18 16:54

【摘要】：目的研究新一代载脂蛋白(apolipoprotein E,apoE)拟肽COG1410的应用对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期脑损伤(early brain injury,EBI)期间大脑自噬及凋亡的影响。方法选用颈内动脉穿刺法建立小鼠SAH模型,首先观察EBI期间伤侧大脑半球自噬、凋亡及相关信号蛋白的表达变化,然后针对自噬水平最活跃的时间点进行COG1410给药,采取Garcia评分评价SAH及给药后小鼠的神经功能变化,利用Western blot测定自噬、凋亡及相关信号分子蛋白的表达量,并使用免疫荧光染色观察皮层神经元的凋亡变化情况。结果 (1)在SAH后EBI期间,与Sham组相比,伤侧大脑半球的自噬水平在SAH后6 h开始增加(P0.05),并在24 h达到高峰(P0.01),随后逐渐下降,信号分子p-GSK-3β水平也有类似的变化趋势;给予小鼠COG1410后,SAH后24 h的大脑自噬活动被进一步增强(P0.05)。(2)在SAH后的EBI期间,伤侧大脑半球整体凋亡水平变化并不完全和自噬及p-GSK-3β水平变化同步,其在EBI后期仍保持相对高值,但有减弱的趋势;给予COG1410后,伤侧大脑半球和皮层神经元凋亡水平均被下调(P0.05)。(3)与Sham组(16.50±1.05)比较,SAH组的Garcia评分(11.17±1.83)明显降低(P0.01),COG1410的干预能显著改善SAH组的Garcia评分(15.17±0.75)(P0.01),但COG1410的干预对SAH分级影响并不大。结论 COG1410的应用可能通过磷酸化GSK-3β增强SAH后EBI期间大脑的自噬活动,减弱神经元的凋亡活动,并改善模型小鼠的神经功能。
[Abstract]:Objective to study the effect of apolipoprotein E peptide COG1410 on cerebral autophagy and apoptosis during early brain injury (early brain injure after subarachnoid hemorrhage. Methods the mouse SAH model was established by internal carotid artery puncture. The changes of autophagy, apoptosis and related signal protein expression in the injured cerebral hemisphere during EBI were observed, and then COG1410 was administered at the most active time point of autophagy. Garcia score was used to evaluate the changes of nerve function in SAH and mice after administration. Autophagy, apoptosis and the expression of related signal molecule protein were measured by Western blot, and apoptosis of cortical neurons was observed by immunofluorescence staining. Results (1) during EBI after SAH, the level of autophagy in the injured hemisphere began to increase at 6 h after SAH (P0.05), reached its peak at 24 h (P0.01), and then decreased gradually. The level of signal molecule p-GSK-3 尾 also showed a similar trend. The cerebral autophagy activity was further enhanced 24 hours after COG1410 administration (P0.05). (2). During EBI after SAH, the changes of global apoptosis in the injured hemisphere were not completely synchronized with the changes of autophagy and p-GSK-3 尾 levels, and remained relatively high at the late EBI stage. But there is a tendency to weaken; after giving COG1410, Compared with Sham group (16.50 卤1.05), the level of neuronal apoptosis in injured cerebral hemisphere and cortex was significantly decreased (P 0.05). The Garcia score of Garcia group (11.17 卤1.83) decreased significantly (P0.01). The Garcia score of SAH group was significantly improved (15.17 卤0.75) (P0.01), but COG1410 intervention had no significant effect on SAH grade. Conclusion the application of COG1410 may enhance the autophagy of the brain during EBI after SAH by phosphorylated GSK-3 尾, attenuate the apoptotic activity of neurons, and improve the neural function of the model mice.
【作者单位】：西南医科大学附属医院神经外科;重庆医科大学附属第一医院神经外科;泸州市人民医院神经外科;
【基金】：国家自然科学基金面上项目(81371319) 泸州市政府-西南医科大学联合项目(2016LZXNYD-Z02,2016LZXNYD-J12)~~
【分类号】：R743.35

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