文章摘要
盐酸戊乙奎醚预处理对小鼠反复缺血-再灌注脑损伤时细胞外信号调节激酶1/2的影响
Effect of penehyclidine hydrochloride preconditioning on extracellular signal-regulated kinase 1/2 during repeated cerebral ischemia-reperfusion injury in mice
  
DOI：10.12089/jca.2019.06.015
中文关键词: 盐酸戊乙奎醚  细胞外信号调节激酶1/2  脑损伤  缺血-再灌注  学习记忆
英文关键词: Penehyclidine hydrochloride  Extracellular signal-regulated kinase 1/2  Cerebral injury  Ischemia-reperfusion  Learning and memory
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作者单位E-mail
杨良民 471003,洛阳市,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科  
谢小娟 471003,洛阳市,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科 lhq_19770812@sina.com 
马立刚 471003,洛阳市,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科  
张永杰 471003,洛阳市,河南科技大学临床医学院,河南科技大学第一附属医院麻醉科  
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中文摘要:
      
目的 探讨盐酸戊乙奎醚预处理对小鼠反复缺血-再灌注(ischemia-reperfusion, IR)脑损伤时细胞外信号调节激酶1/2（ERK1/2）的影响。
方法 SPF级成年C57BL/6J小鼠96只，6～8周龄，体重16～25 g，按照随机数字表法分为三组：盐酸戊乙奎醚组(PHC组)、IR组和假手术组(Sham组)，每组32只。Sham组腹腔注射等容量生理盐水，30 min后分离双侧颈总动脉但不夹闭；IR组腹腔注射等容量生理盐水，30 min后分离并夹闭双侧颈总动脉，建立反复IR脑损伤模型；PHC组腹腔注射盐酸戊乙奎醚1.0 mg/kg，30 min后采用双侧颈总动脉夹闭术建立反复IR脑损伤模型。采用Morris水迷宫实验评估术前及术后学习记忆能力，随后处死小鼠，留取海马组织并测定其湿/干重比(W/D)。采用伊文斯蓝(EB)法检测血脑屏障的通透性。采用逆转录-聚合酶链式反应(RT-PCR)测定海马组织ERK1/2 mRNA表达量，Western blot法测定海马组织磷酸化ERK1/2(p-ERK1/2)蛋白含量。
结果 与Sham组比较，术后3、7 d IR组逃避潜伏期和游泳距离明显延长(P<0.05)。与IR组比较，术后3、7 d PHC组逃避潜伏期和游泳距离明显缩短(P<0.05)。与Sham组比较，IR组海马组织W/D和脑组织EB含量明显升高(P<0.05)。与IR组比较，PHC组海马组织W/D和脑组织EB含量明显降低(P<0.05)。与Sham组比较，IR组海马组织ERK1/2 mRNA表达量和p-ERK1/2蛋白含量明显升高(P<0.05)。与IR组比较，PHC组海马组织ERK1/2 mRNA表达量和p-ERK1/2蛋白含量明显降低(P<0.05)。
结论 盐酸戊乙奎醚预处理可通过抑制海马组织ERK 1/2激活而减轻小鼠反复缺血-再灌注脑损伤并改善其学习记忆能力。
英文摘要:
      
Ojective To investigate the effect of penehyclidine hydrochloride preconditioning on extracellular signal-regulated kinase 1/2 during repeated cerebral ischemia-reperfusion (IR) injury in mice.
Methods Ninety-six C57BL/6J mice, graded into specific pathogen free (SPF), aged 6 - 8 weeks, weighing 16 - 25 g, were randomly allocated into three groups as follows: penehyclidine hydrochloride group (group PHC), group IR and sham operation group (group Sham), 32 mice in each group. Mice were intraperitoneally injected with normal saline, and the bilateral common carotid arteries were separated but not clamped after 30 min in group Sham. Mice were intraperitoneally injected with normal saline, and after 30 min, the bilateral common carotid arteries were isolated and clamped to establish a model of repeated IR brain injury in group IR. Mice were injected intraperitoneally with penehyclidine hydrochloride at a dose of 1.0 mg/kg, and after 30 min bilateral common carotid arteries were clipped for establishing the model of repeated IR cerebral injury in group PHC. Learning and memory function of mice were tested by Morris water maze test before and after surgery. After Morris water maze test, mice were euthanized, and hippocampus was excised. The ratio of wet weight to dry weight (W/D) of hippocampus was tested. The permeability of blood-brain barrier was determined by Evans blue (EB) method. The expression levels of extracellular signal-regulated kinase 1/2 (ERK1/2) mRNAs in hippocampus were determined by reverse transcription-polymerase chain reaction (RT-PCR). The expression levels of phosphorylated (p-ERK1/2) proteins in hippocampus were detected by Western blot.
Results Compared with group Sham, the escape latency and swimming distance of mice were prolonged 3 and 7 d after surgery in group IR (P < 0.05). Compared with group IR, the escape latency and swimming distance of mice were shortened 3 and 7 d after surgery in group PHC (P < 0.05). Compared with group Sham, hippocampal W/D and the content of EB of brain tissue were higher in group IR (P < 0.05). Compared with group IR, hippocampal W/D and the content of EB of brain tissue were lower in group PHC (P < 0.05). Compared with group Sham, the expression levels of ERK1/2 mRNA and protein in hippocampus were higher in group IR (P < 0.05). Compared with group IR, the expression levels of ERK1/2 mRNA and protein in hippocampus were lower in group PHC (P < 0.05).
Conclusion Penehyclidine hydrochloride can alleviate cerebral injury and improve learning and memory function of mice with repeated cerebral IR injury via inhabiting the activation of ERK1/2 in hippocampus.
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