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β-APP和NF-L在评估弥漫性轴索损伤大鼠损伤程度中的价值

, PP. 2255-2260

Keywords: 弥漫性轴索损伤,免疫组织化学,&beta,-淀粉样前体蛋白,神经丝蛋白轻链多肽,水迷宫,大鼠

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Abstract:

目的利用自制装置建立轻、中、重度的弥漫性轴索损伤(diffuseaxonalinjury,DAI)大鼠模型,观察不同时间点β-淀粉样前体蛋白(β-amyloidprecursorprotein,β-APP)及神经丝蛋白轻链多肽(neurofilamentlightpolypeptide,NF-L)的变化与恢复期的学习记忆能力的相关性。方法健康成年SD大鼠100只,随机分为正常对照组和A、B、C(轻、中、重型致伤)DAI组。伤后6、24、72h及1、2周取脑组织切片行β-APP免疫组织化学染色;24h时脑组织切片行HE染色和NF-L免疫组织化学染色;2周时行水迷宫测试。将损伤后24h各组脑组织切片感兴趣区内测定的β-APP和NF-L累积光密度(IOD)值与损伤后恢复期大鼠的学习记忆能力做相关性分析。结果伤后24h取脑组织肉眼观察致伤组大脑表面、蛛网膜下腔、脑室等区域未见出血,光镜下可见A、B、C组大鼠的胼胝体区神经束疏松、紊乱,血管淤滞,空泡形成,神经元肿胀变性,细胞核显示不清,突触结构模糊等经典DAI病理特征,NF-L免疫组化鉴定实验组均有典型中线部位轴索损伤改变。实验组伤后6、24、72h及1、2周与对照组相比各时间点胼胝体β-APP均有升高(P<0.05),组内各时间点呈动态变化,于伤后24h最高。伤后24h,实验组NF-L免疫组化染色大脑水管水平脑干轴突和神经元胞体阳性染色较正常组增强,半定量分析A、B、C3组间差异有统计学意义(P<0.05)。水迷宫测试与正常对照组比较,A组大鼠学习记忆功能无明显下降;B、C两组下降明显(P<0.05)。损伤后24h,A、B、C3组脑组织切片感兴趣区内测定的β-APP和NF-L累积光密度(IOD)值与损伤后恢复期大鼠的学习记忆能力呈负相关(r分别为-0.937、-0.939)。结论β-APP和NF-L不仅可以反映DAI动物模型轴索损伤的程度,还可以早期预测损伤后大鼠的学习记忆恢复能力,可能成为DAI损伤的特异性分子探针。

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