TAT-XIAP融合蛋白对学习记忆障碍大鼠的影响及其机制

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目的 探讨TAT-XIAP融合蛋白对学习记忆障碍大鼠的影响及其与大脑海马神经元凋亡的关系,为学习记忆的深入研究提供实验依据.方法 利用基因工程技术制备具有生物学活性的TAT-XIAP融合蛋白,通过D-半乳糖(D-Gal)腹腔注射和Aβ1-42海马注射建立学习记忆障碍大鼠模型,将大鼠随机分为TAT-XIAP组(左侧脑室注射TAT-XIAP融合蛋白,每天80 mg/kg,共3d)和模型组(侧脑室注射等体积PBS)各30只,采用水迷宫评价大鼠的学习记忆能力,TUNEL法检测大鼠海马神经元凋亡.结果 1TAT-XIAP组大鼠在各象限入水至爬上平台的时间均明显缩短,平均值为(48.31±9.44)s,明显低于模型组的(87.80±10.32)s(P<0.05);TAT-XIAP组大鼠穿越平台的次数、在原平台象限游程百分比、在原平台象限时间百分比均明显增加,分别为(4.78±0.93)次、(47.39±5.84)%、(48.43±5.75)%,与模型组比较,差异有统计学意义(P<0.05).2 TAT-XIAP组大鼠海马凋亡神经元明显减少,凋亡神经元计数为(16.37±3.15)个/mm2,模型组为(54.66±7.20)个/mm2,两者差异有统计学意义(P<0.05).结论 TAT-XIAP融合蛋白可明显改善学习记忆障碍大鼠学习记忆功能,其机制可能与大鼠海马神经元凋亡减少有关.“,”Objective To investigate the TAT-XIAP fusion protein on learning and memory impairment in rats and its relationship with the brain hippocampus neuron apoptosis,and to provide experimental evidence for the in-depth study of learning and memory.Methods Using genetic engineering technology to prepare biologically active fusion protein TAT-XIAP,D-galactose (D-Gal) by intraperitoneal injection and Aβ1-42 by hippocampal injection,rat model was established by injection of learning and memory impairment.The rats were randomly divided into TAT-XIAP groups (left lateral cerebral ventricle injection of TAT-XIAP fusion protein,80 mg/kg per day,3 days) and model group (lateral cerebral ventricle injection of an equal volume of PBS),each group 30 rats.Learning and memory of rats were measured by water maze,and rat hippocampal neuronal apoptosis were measured by TUNEL assay.Results The time was significantly shorter into the water to climb up platform in each quadrant of TAT-XIAP rats,with an average of (48.31 ± 9.44)s,and it was significantly lower than the model group((87.80± 10.32) s,P < 0.05).The number through the platform,target quadrant swim away a percentage and time in the target quadrant percentage were significantly increased in TAT-XIAP group rats(respectively,4.78 ±0.93,(47.39± 5.84) %,(48.43 ± 5.75) %).It was significant difference with the model group comparison (P < 0.05).Apoptosis of neuron reduced significantly in hippocampus of TAT-XIAP group rats,apoptosis of neuron count was 16.37±3.15 pieces per square millimeter,and model group was 54.66 ± 7.20 pieces per square millimeter.It was significant difference compared by statistical analysis(P <0.05).Conclusion TAT-XIAP fusion protein can significantly improve learning and memory function of learning and memory impairment in rats,which may be related to decreasing neurons apoptosis in hippocampus.
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