创伤性脑损伤后tau蛋白磷酸化水平动态变化及意义

被引:3
作者
赵子艾
宁亚蕾
杨楠
彭艳
熊仁平
陈惺
白伟
周元国
机构
[1] 第三军医大学附属大坪医院野战外科研究所分子生物学中心,创伤,烧伤与复合伤国家重点实验室
关键词
脑损伤; tau蛋白质类; 认知功能障碍;
D O I
暂无
中图分类号
R651.1 [颅脑];
学科分类号
摘要
目的研究小鼠创伤性脑损伤(traumatic brain injury,TBI)后急性期、亚急性期及慢性期tau蛋白磷酸化水平动态变化规律。方法采用可控皮质打击方法建立小鼠中度TBI模型,无特定病原体(specific pathogen free,SPF)级C57BL/6雄性小鼠40只按随机数字表法分为创伤组、假手术组,创伤组又分为3个亚组:24 h、7 d及1个月组,每组10只。采用免疫组化方法检测伤后24 h、7 d、1个月脑组织tau蛋白磷酸化水平变化、胶质细胞增生程度、神经元丢失及淀粉样肽前体蛋白(amyloid precursor protein,APP)标记的轴突损伤。结果创伤24 h、7 d、1个月组对侧海马齿状回区tau蛋白Ser404位点磷酸化水平分别为4 451.021±471.731,5 339.826±794.071,1 906.036±369.808,均较假手术组368.630±231.038明显升高(t=23.316,18.033,9.979,P<0.01)。而其余Thr205、Ser262位点磷酸化水平未见明显改变。胶质纤维酸性蛋白(glial fibrous acid protein,GFAP)免疫组化染色结果显示,刨伤24 h、7 d组吸光度(A)值分别为30 495.233±6 174.094,86 427.920±11 896.771,均显著高于假手术组6 825.653±3 451.641(t=9.573,9.573,P<0.01),而创伤1个月组9 511.471±5 431.077与假手术组比较差异无统计学意义(t=1.181,P>0.05)。APP免疫组化结果显示,假手术组、创伤24 h、7 d及1个月组A值分别为459.061±368.608,1 802.695±491.938,2 762.852±636.524,2 333.118±511.731,创伤组均高于假手术组(t=5.684,7.960,7.697,P<0.01)。各时相点NeuN标记神经元计数结果显示,对侧齿状回区神经元在创伤24 h组与假手术组[(290.056±39.162):(314.019±42.397)]差异无统计学意义(t=-1.017,P>0.05),创伤7 d、1个月组分别为250.509±17.592,242.717±17.045,均少于假手术组(t=-3.112,-3.506,P<0.01)。结论 TBI后tau蛋白Ser404位点磷酸化水平长期升高可能与TBI后慢性期认知功能障碍有关。
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页码:344 / 348
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