摘要
目的探讨缺血后处理对大鼠局灶性脑缺血/再灌注损伤的保护作用及与内质网应激通路相关分子GRP78、caspase-12的关系。方法成年雄性Wistar大鼠58只,随机分为假手术组(sham组)、缺血/再灌注组(I/R组)和缺血后处理组(IP组),采用线栓法阻断大脑中动脉制备大鼠局灶性脑缺血/再灌注(MCAO)模型。大鼠脑缺血/再灌注后24 h进行神经行为学评分和脑梗死体积测定;脑缺血/再灌注6 h、12 h、24 h后免疫组织化学方法检测脑缺血侧半暗带区GRP78、caspase-12蛋白的表达。结果与缺血/再灌注组相比,后处理组再灌注24h神经行为学评分明显降低,脑梗死体积明显减少(P<0.05);后处理组再灌注12 h、24 h GRP78蛋白表达明显增加,再灌注24 h caspase-12蛋白表达明显减少。结论脑缺血后处理可能通过减弱内质网应激过程从而对随后发生的再灌注损伤起到了神经保护作用。其机制可能是增加GRP78蛋白表达、减少caspase-12蛋白表达而减轻神经细胞的凋亡。
Objective To study the protective effect of ischemic postconditioning on focal cerebral ischemic/reperfu- sion injury in rats and to discuss the relationship with endoplasmic reticulum stress related moleculars GRP78 ,caspase-12. Methods Adult male Wistar rats were randomly divided into three groups for the experiment：Sham group,ischemic/reper- fusion group（ I/R group）and isehcmic postconditioning group（ IP group）. Focal cerebral ischemia/repeffusion model was induced by suture-occluded method to establish middle cerebral artery occlusion（MCAO）. Then,the neurobehavioral scores and cerebral infarct volume were measured at 24h of repeffusion, and the expression of GRP78 ,caspase-12 proteins in the ischemic penumbra were detected by immunohistochemistry from 6h to 24h of repeffusion. Results In the ischemic post- conditioning group,the neurobehavioral scores and cerebral infarct volume reduced significantly（P 〈0.05）. In comparison to the ischemic/repeffusion group, the expression of GRP78 protein were significantly increased in the postconditiouing group rats from 12 h to 24 h of repeffusion（ P 〈 0.05 ） , and the expression of caspase-12 significantly reduced in the post- conditioning group rats at 24 h of repeffusion （ P 〈 0.05 ）. Conclusions Cerebral ischemic postconditioning protects brain against ischemia/repeffusion injury by attenuating endoplasmic reticulum stress induced apoptosis. The possible mechanism might be that it can increase GRP78 and attenuate caspase-12 expression.
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2014年第3期203-206,共4页
Journal of Apoplexy and Nervous Diseases
基金
吉林省财政厅卫生专项项目(项目号:3D512W133428)
