GRP78、CHOP、caspase-3和caspase-9蛋白在缺血预处理大鼠脑组织中的表达及意义  

Expression and significance of GRP78,CHOP,caspase-3 and caspase-9 proteins in preconditioning focal cerebral ischemia in rats

作　　者：闵鹤鸣[1] 鲁璐清[1] 王文娟[2] 武晓宁[2] 闵连秋[2] 

机构地区：[1]辽宁医学院基础医学院,辽宁锦州121000 [2]辽宁医学院附属第一医院神经内科,辽宁锦州121001

出　　处：《中风与神经疾病杂志》2012年第8期703-706,共4页Journal of Apoplexy and Nervous Diseases

基　　金：辽宁医学院奥鸿大学生创新课题基金项目;辽宁省自然科学基金项目(20092192)

摘　　要：目的探讨GRP78、CHOP、caspase-3和caspase-9蛋白在缺血预处理大鼠脑组织中的表达及意义。方法 SD大鼠随机分为脑缺血预处理、2-脱氧葡萄糖(2-deoxyglucose,2-DG)预处理组、脑缺血/再灌注组和对照组,2-DG预处理组于术前7d腹腔注射2-DG 100mg.kg-1.d-1,采用线栓法阻断大脑中动脉制备大鼠局灶性脑缺血/再灌注模型,然后进行神经行为学评分、脑梗死体积和脑含水量测定,免疫组织化学方法检测缺血区脑组织GRP78、CHOP、caspase-3和caspase-9蛋白的表达。结果与缺血/再灌注组相比,预处理缺血组和2-DG预处理组神经行为学评分明显降低,脑梗死体积和脑组织含水量明显减少(P<0.01,P<0.05),GRP78蛋白表达细胞数明显增加(P<0.01),CHOP、caspase-3和caspase-9蛋白表达的细胞数明显减少(P<0.01);而两组间比较无统计学差异(P>0.05)。结论脑缺血预处理可能触发了体内的内质网应激过程,对随后发生缺血/再灌注所造成损伤的具有神经保护作用。其机制可能是增加GRP78蛋白的表达和降低CHOP、caspase-3和caspase-9蛋白的表达,减轻了神经细胞的凋亡。Objective To study the expression and significance of GRP78,CHOP,caspase-3 and caspase-9 in preconditioning focal cerebral ischemia in rats.Methods In this experiment,Sprague-Dawley（SD） rats were randomly divided into cerebral ischemia preconditioning,2-deoxyglucose（2-deoxyglucose,2-DG） preconditioning group,cerebral ischemia-reperfusion group and control group.2-DG preconditioning group was injected the 2-DG 100mg·kg-1·d-1 in the peritoneal cavity for 7 days before surgery.Middle cerebral artery（MCA） of the SD rats were blocked by suture-occluded method to establish preconditioning cerebral ischemia model and focal cerebral ischemia-reperfusion model.Then,the neurobehavioral scores,cerebral infarct volume and brain water content were measured,and the expressions of GRP78,CHOP,caspase-3 and caspase-9 proteins in the brain tissue of rats were detected by immunohistochemistry.Results In the cerebral ischemia preconditioning group and the 2-DG preconditioning group,the neurobehavioral scores,cerebral infarct volume and brain water content reduced significantly（P0.01,P0.05）.The cells expression of GRP78 protein increased clearly（P0.01）,and the express of CHOP,caspase-3 and caspase-9 proteins decreased obviously（P0.01）,compared with ischemia-reperfusion group.While no significant difference between the cerebral ischemia preconditioning group and the 2-DG preconditioning group（P0.05） was found.Conclusion The cerebral ischemic preconditioning may trigger endoplasmic reticulum stress in vivo process,and has a neuroprotective effect after ischemic-reperfusion damage.The possible mechanism is that cerebral ischemia preconditioning can increase the expression of GRP78 protein and decrease the expression of CHOP,caspase-3 and caspase-9 protein expression,and reduce the apoptosis of neural cells.

关 键 词：脑缺血预处理 GRP78 CHOP CASPASE-3 CASPASE-9 

分 类 号：R743[医药卫生—神经病学与精神病学]