【摘要】 本文探讨热应激预处理对脑缺血小鼠海马神经元保护作用的可能机制。以72只6月龄昆明小鼠为研究对象,热应激预处理小鼠,随后夹闭双侧颈总动脉7min后再通制成脑缺血/再灌注损伤模型。根据不同的处理方法将动物随机分为四组:(1)正常对照组,(2)热应激预处理后缺血再灌注组(HS/IR),(3)缺血再灌注组(IR),(4)热应激组(HS)。将HS组、IR组和HS/IR组又分为1d、4d、14d3个亚组。用免疫组织化学及图像分析方法观察热应激对环磷酸腺苷反应元件结合蛋白(CREB)以及降钙素基因相关肽(CGRP)表达的影响。结果表明,与正常对照组比较,HS、HS/IR、IR组小鼠海马CREB表达明显增多(P<0.05)。热应激可诱导CGRP的分泌和在脑内的重分布,和其他组比较,CGRP在4dHS/IR组增多的最为明显(P<0.01)。热应激后,光镜下可见CGRP免疫阳性产物出现在海马CA1区的曲张纤维和神经元的核周质。以上实验结果提示,脑缺血状态下热应激的保护作用可能是通过激活信号蛋白CREB进而促进内源性保护物质CGRP释放而实现。更多还原

【Abstract】 The present study was to explore the mechanism of heat stress on protecting the neurons in hippocampal CA1 regions of ischemic mouse model. Six-month-old mice (n=72)were used to be pretreated with heat stress subsequent to ischemia/ reperfusion by clipping bilateral cervical common arteries for 7 min. According to different treatments, animals were divided randomly into 4 groups: (1) normal control group; (2) heat stress pretreatment followed by ischemia and reperfusion group (HS/IR);(3) ischemia and reperfusion group (IR) (4) heat stress group (HS). Animals in the later three groups were subdivided into 3 subgroups (1 d, 4 d, 14 d), respectively. The changes of the expression of cAMP response element binding protein(CREB) and calcitonin gene-related peptide(CGRP)were detected by immunohistochemistry and computer image analysis methods. The results showed that compared with normal group, the expressions of CREB in hippocampal CA1 region increased significantly in HS, HS/IR and IR groups (P<0.05). Compared to normal group, heat stress could result in CGRP excretion and redistribution in cerebrum with a highest level in 4 d HS/IR group. Following heat stress, CGRP immunoreactivity was observed in varicose fibers and neuronal perikarya within CA1 region. The results indicate that heat stress can induce CGRP excretion through CREB signal pathway and thus to exert protective roles for hippocampal neurons under ischemic condition.更多还原