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p38 MAPK 信号通路对新生大鼠缺氧缺血性脑损伤后认知功能及神经元功能恢复的影响。

Effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury in newborn rats.

机构信息

Departments of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.

Departments of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.

出版信息

J Clin Neurosci. 2020 Aug;78:365-370. doi: 10.1016/j.jocn.2020.04.085. Epub 2020 Apr 30.

Abstract

To explore the effects of p38 MAPK signaling pathway on cognitive function and recovery of neuronal function after hypoxic-ischemic brain injury (HIBI) in newborn rats. Seventy-two healthy SPF grade SD newborn rats were randomly and equally divided into Normal group (healthy rats) and Sham group (rats underwent sham operation), Model group (HIBI model rats), p38 MAPK Inhibitor group (HIBI model rats treated with p38 MAPK inhibitor) and p38 MAPK Activator group (HIBI model rats treated with p38 MAPK activator). On postnatal day 28, Morris water maze, tail suspension test and inclined plane test were conducted on rats in each group. Twenty-four hours after modeling, the expression of p-p38 MAPK protein and apoptosis related genes in rat hippocampal tissues was detected by TUNEL staining, qRT-PCR and Western blot. Compared with Normal group, escape latency and inclined plane test time were prolonged, the number of passing through the platform and tail suspension time were reduced (all P < 0.05); Bax and Caspase-3 mRNA and protein expression levels and p-p38 MAPK protein level were increased, Bcl-2 mRNA level was decreased, and neuronal apoptosis proportion was increased in Model group (all P < 0.05). Compared with Model group, the above indicators showed reversed and enhanced trends in p38 MAPK Inhibitor and p38 MAPK Activator groups, respectively (all P < 0.05). Inhibition of p38 MAPK signaling pathway can effectively improve the learning and memory ability and motor function of newborn rats with HIBI, and reduce neuronal apoptosis in the hippocampal tissues, thereby promoting neuronal recovery.

摘要

探讨 p38MAPK 信号通路对新生大鼠缺氧缺血性脑损伤(HIBI)后认知功能和神经元功能恢复的影响。将 72 只健康 SPF 级 SD 新生大鼠随机均分为正常组(健康大鼠)和假手术组(大鼠接受假手术)、模型组(HIBI 模型大鼠)、p38MAPK 抑制剂组(HIBI 模型大鼠给予 p38MAPK 抑制剂处理)和 p38MAPK 激活剂组(HIBI 模型大鼠给予 p38MAPK 激活剂处理)。造模后 28 天,对各组大鼠进行 Morris 水迷宫、悬尾实验和斜板实验。造模 24 小时后,采用 TUNEL 染色、qRT-PCR 和 Western blot 法检测大鼠海马组织中 p-p38MAPK 蛋白及凋亡相关基因的表达。与正常组比较,模型组逃避潜伏期和斜板实验时间延长,穿过平台次数和悬尾时间减少(均 P<0.05);Bax、Caspase-3mRNA 及蛋白表达水平和 p-p38MAPK 蛋白水平升高,Bcl-2mRNA 水平降低,神经元凋亡比例增加(均 P<0.05)。与模型组比较,p38MAPK 抑制剂组和 p38MAPK 激活剂组上述指标呈现相反和增强趋势(均 P<0.05)。抑制 p38MAPK 信号通路可有效改善新生大鼠 HIBI 后学习记忆能力和运动功能,减少海马组织神经元凋亡,从而促进神经元恢复。

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