论文部分内容阅读
目的:探讨细胞外信号调节激酶(ERK)通路在脑缺血及缺血预处理海马神经元中的作用。方法:雄性蒙古沙土鼠,随机分为假手术组(SH)、缺血/再灌注组(I/R)、缺血预处理组(IP)、PD98059组(PD)、溶剂对照组(VE组)、PD98059复合IP组(PIP),每组按再灌注15 min、2 h、4 h、6 h、1 d、3 d、5 d及7 d又分8个亚组。建立前脑缺血再灌注损伤模型,观察对行为学、组织学、p-ERK、HSP70、Fos及NF-κB表达的影响。结果:IP组鼠探索活动、CA1区凋亡神经元数及NF-κB阳性神经元数较I/R组明显减少(P<0.05),CA1区Fos阳性神经元数、HSP70及CA3/DG区p-ERK表达水平较I/R组明显增加(P<0.05)。PD组再灌注各点Fos阳性神经元数较I/R组明显减少(P<0.05)。再灌注1 d、3 d凋亡神经元数较I/R组明显增多(P<0.05)。PIP组各观察指标介于IP组及IR组间。结论:ERK通路在缺血后海马CA3/DG区的激活可能与该区的缺血耐受有关;诱导CA1区神经元Fos、HSP70表达,减少NF-κB生成是缺血预处理神经元保护作用的分子机制之一。
AIM: To investigate the role of extracellular signal-regulated kinase (ERK) pathway in preconditioning of hippocampal neurons with cerebral ischemia and ischemia. Methods: Male Mongolian gerbils were randomly divided into sham operation group (SH), ischemia / reperfusion group (I / R), ischemic preconditioning group (IP), PD98059 group (PD), solvent control group ) And PD98059 compound IP group (PIP). Each group was divided into 8 subgroups according to 15 min, 2 h, 4 h, 6 h, 1 d, 3 d, 5 d and 7 d after reperfusion. The model of forebrain ischemia-reperfusion injury was established and the effects on behavior, histology, expression of p-ERK, HSP70, Fos and NF-κB were observed. RESULTS: In IP group, the number of apoptotic neurons and the number of NF-κB positive neurons in CA1 area were significantly lower than those in I / R group (P <0.05). The numbers of Fos positive neurons, HSP70 and CA3 / DG The expression of p-ERK was significantly higher than that of the I / R group (P <0.05). The number of Fos positive neurons in PD group was significantly decreased compared with I / R group (P <0.05). The numbers of apoptotic neurons on day 1 and 3 after reperfusion were significantly higher than those in I / R group (P <0.05). PIP group between the observation index between the IP group and IR group. CONCLUSION: The activation of ERK pathway in the hippocampal CA3 / DG area may be related to the ischemic tolerance of the hippocampus. The induction of Fos and HSP70 expression in the CA1 neurons and the decrease of the NF-κB production are neuroprotective effects of ischemic preconditioning One of the molecular mechanisms.