MAPKs阻滞剂U0126对创伤性脑损伤大鼠学习记忆功能的影响及机制探讨

发布时间：2019-01-17 17:28

【摘要】：目的观察丝裂原活化蛋白激酶(MAPKs)阻滞剂U0126对创伤性脑损伤(TBI)大鼠学习记忆功能的影响,并探讨其机制。方法将313只成年雄性SD大鼠随机分为假手术组52只、模型组87只、DMSO组87只、U0126组87只,除假手术组外其余各组制备大鼠弥漫性脑创伤模型。U0126组将0.1 mg/kg U0126以0.1 mmol/L的PBS稀释至300μL,于造模前30 min尾静脉注射。DMSO组同时点尾静脉注射相同含量DMSO稀释溶液,假手术组和模型组同时点尾静脉注射生理盐水300μL。造模30 min、3 h、12 h、24 h、48 h、72 h、7 d取各组大鼠各5只(假手术组3只),采用TUNEL法观察各组海马组织神经细胞凋亡情况。造模30 min、3 h、12 h、24 h、48 h、72 h、7 d取各组大鼠各6只(假手术组3只),采用Western blot法检测各组海马组织磷酸化细胞外信号调节激酶1/2(p-ERK1/2)蛋白表达。造模14、16、18、21 d取各组大鼠各10只,采用Morris水迷宫实验观察大鼠空间学习记忆能力。结果造模48、72 h时,U0126组海马组织神经细胞凋亡数少于DMSO组、模型组,P均0.05;造模24、48、72 h时,U0126组、DMSO组、模型组海马组织神经细胞凋亡数均多于假手术组,P均0.05;造模48、72 h时,U0126组海马组织p-ERK1/2蛋白相对表达量低于模型组、DMSO组,P均0.05;造模12、24、48、72 h时,U0126组、DMSO组、模型组海马组织p-ERK1/2蛋白相对表达量均短于假手术组,P均0.05;造模16、18、21 d时U0126组大鼠潜伏期均短于DMSO组、模型组,P均0.05;造模14、16、18、21 d时U0126组、DMSO组、模型组大鼠潜伏期均长于假手术组,P均0.05。相关性分析结果显示,海马区神经细胞凋亡数与p-ERK1/2表达呈正相关(r=0.468,P=0.002)。结论 U0126可抑制TBI大鼠海马神经细胞凋亡,提高大鼠的学习记忆能力,可能与降低海马组织中pERK1/2表达有关。
[Abstract]:Objective to investigate the effects of U0126, a mitogen-activated protein kinase (MAPKs) blocker, on learning and memory function in (TBI) rats with traumatic brain injury. Methods 313 adult male SD rats were randomly divided into sham-operated group (n = 52), model group (n = 87), DMSO group (n = 87) and U0126 group (n = 87). The model of diffuse brain trauma was established in rats in each group except sham-operation group. Group U0126 diluted 0.1 mg/kg U0126 to 300 渭 L with 0.1 mmol/L PBS. 30 min before the model, the DMSO group was injected with the same amount of DMSO diluted solution, and the sham operation group and the model group were injected with 300 渭 L saline simultaneously. The apoptosis of hippocampal nerve cells in each group was observed by TUNEL method. Five rats in each group (3 rats in sham-operation group) were taken from each group for 7 days after 30 min,3 / 12 h and 48 h / 48 h and 72 h / d respectively. The apoptosis of hippocampal nerve cells in each group was observed by TUNEL method. Six rats in each group (3 rats in sham-operation group) were taken for 7 days. The expression of extracellular signal regulated kinase 1 / 2 (p-ERK1/2) protein in hippocampal tissue was detected by Western blot assay. The spatial learning and memory ability of rats in each group was observed by Morris water maze experiment. Results the number of neuronal apoptosis in hippocampal tissue of U0126 group was lower than that of DMSO group (P 0.05), and that of U0126 group, DMSO group and model group was more than that of sham operation group (P 0.05). The relative expression of p-ERK1/2 protein in hippocampal tissue of U0126 group was lower than that of model group and DMSO group (P 0.05). The relative expression of p-ERK1/2 protein in hippocampal tissue of U0126 group, DMSO group and model group was shorter than that of sham operation group (P 0.05), and the latency of U0126 group was shorter than that of DMSO group (P 0.05). The latencies of U0126 group, DMSO group and model group were longer than those of sham operation group (P 0.05). The results of correlation analysis showed that the number of neuronal apoptosis in hippocampus was positively correlated with the expression of p-ERK1/2 (r 0. 468 P0. 002). Conclusion U0126 can inhibit the apoptosis of hippocampal neurons and improve the learning and memory ability of TBI rats, which may be related to the decrease of pERK1/2 expression in hippocampus.
【作者单位】：唐山市工人医院;华北理工大学基础医学院;
【基金】：河北省自然科学基金资助项目(H2012401071) 河北省引进留学人员资助项目(2012-02)
【分类号】：R651.15

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