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大鼠弥漫性轴索损伤后高迁移率族蛋白1的动态表达及其对神经细胞凋亡的影响
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大鼠弥漫性轴索损伤后高迁移率族蛋白1的动态表达及其对神经细胞凋亡的影响
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Journal Article
大鼠弥漫性轴索损伤后高迁移率族蛋白1的动态表达及其对神经细胞凋亡的影响
2015
Overview
目的研究高迁移率族蛋白1（HMGB-1）在弥漫性轴索损伤（DAI）后脑组织内的动态表达及其对神经细胞凋亡的影响,探讨其参与DAI后脑组织炎症反应的机制。方法采用大鼠头颅瞬间旋转装置制备大鼠DAI模型,通过组织病理学方法评价DAI模型的稳定性,采用免疫组化、Western blot、RT-PCR等方法分别于造模后6h,1、3、7d为时间点,测定DAI后HMGB-1的表达及分布变化,并采用TUNEL试剂盒进一步观察DAI后神经元的凋亡。结果免疫组化结果显示,在DAI后6h及1d,大鼠皮层脑组织中HMGB-1阳性细胞数呈下降趋势,但是3d后开始明显增多;Western blot结果证实,DAI后早期（6h、1d）,皮层脑组织中HMGB-1蛋白水平较对照组显著降低,然而在DAI后3d出现明显升高,一直持续至第7天;RT-PCR显示,DAI后早期（6h）HMGB-1mRNA水平并无明显增加,DAI后1d仅有轻度增加,DAI后3dHMGB-1mRNA水平才开始明显升高。TUNEL结果显示,在DAI后6h神经元凋亡已明显增加,并呈持续增加趋势,DAI后3d达到高峰,一直持续至DAI后7d仍处于较高水平。结论大鼠DAI后脑组织内HMGB-1表达呈逐渐升高的动态变化,其脑组织总蛋白水平早期（6h、1d）降低,可能由坏死神经元释放及基因转录水平较低所致,而晚期（3、7d）明显升高,可能是胶质细胞活化诱导基因表达升高所致,HMGB-1与神经元凋亡并无直接相关性,其可能通过诱导炎症反应间接参与DAI后的神经元凋亡。
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