摘要
为了揭示突触后密度蛋白-95抑制剂Tat-NR2B9c(NA-1)对新生儿缺氧缺血性脑损伤动物模型的保护作用,本研究将60只7日龄SD大鼠随机分为假手术组、模型组和NA-1组。在建立缺氧缺血性脑损伤模型1 h后,NA-1组按照20μg/g的剂量在大鼠腹膜内注射NA-1溶液,模型组和假手术组注射等体积的生理盐水。TTC染色显示,在建立缺氧缺血性脑损伤大鼠模型24 h后,NA-1处理可显著降低大鼠的脑梗死体积(p<0.05)。此外,建模7 d后,应用NA-1处理的大鼠的悬崖逃避反射、趋地反射和翻正反射时间均显著低于模型组(p<0.05)。Nissl染色显示,建模3 d时,应用NA-1处理的大鼠的存活的神经元数量明显升高(p<0.05)。TUNEL染色结果显示,NA-1处理的大鼠的神经细胞凋亡数量明显低于模型组(p<0.05)。Western blotting显示,NA-1处理可显著降低NA-1组大鼠脑组织的caspase-3蛋白表达水平,并上调大鼠脑组织中p-Akt/t-Akt的蛋白比率(p<0.05)。本研究表明,NA-1能够有效降低新生缺氧缺血性脑损伤大鼠的脑梗死体积,改善大鼠神经行为,抑制神经细胞凋亡。NA-1还可通过激活PI3K/Akt信号通路来提供神经保护作用。
To reveal the protective effect of the postsynaptic density protein-95 inhibitor Tat-NR2B9c(NA-1)on neonatal hypoxic-ischemic brain damage.In this study,607-day-old SD rats were randomly divided into sham operation group,model group and NA-1 group.One hour after the establishment of hypoxic-ischemic brain injury model,NA-1 group was intraperitoneally injected with NA-1 solution at a dose of 20μg/g.The model group and the sham operation group were injected with an equal volume of normal saline.TTC staining showed that NA-1 treatment significantly reduced cerebral infarction volume in rats after establishing hypoxic-ischemic brain damage in rats for 24 h(p<0.05).In addition,after 7 days of modeling,the cliff escape reflex,geotaxis reflex and righting reflex time of rats treated with NA-1 were significantly lower than the model group(p<0.05).Nissl staining showed that the number of surviving neurons in the NA-1 treated rats was significantly increased(p<0.05)when modeled 3 d.TUNEL staining showed that the number of neuronal apoptosis in NA-1 treated rats was significantly lower than that in the model group(p<0.05).Western blotting showed that NA-1 treatment significantly decreased the expression of caspase-3 protein in brain tissue of rats in the NA-1 group,and up-regulated the protein ratio of p-Akt/t-Akt in rat brain tissue(p<0.05).This study demonstrates that NA-1 can effectively reduce the cerebral infarction volume of rats with hypoxic-ischemic brain damage,improve neurobehavior and inhibit neuronal apoptosis.NA-1 also provides neuroprotection by activating the PI3 K/Akt signaling pathway.
作者
袁二伟
曲海新
张雅静
许津莉
王玲玲
Yuan Erwei;Qu Haixin;Zhang Yajing;Xu Jinli;Wang Lingling(The First Affiliated Hospital of Hebei North University,Zhangjiakou,075000)
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2020年第5期2245-2251,共7页
Genomics and Applied Biology
