Apelin-13对鼠脑缺血-再灌注后的作用及机制  

Effect and mechanism of apelin-13 on cerebral ischemia-reperfusion injury in mice

作　　者：杨燚[1] 崔海瑛[1] 祝春华[1] 张聪[1] 苗江永[1] 

机构地区：[1]河北医科大学第二医院神经内科,河北省神经病学重点实验室,石家庄050000

出　　处：《脑与神经疾病杂志》2015年第6期401-408,共8页Journal of Brain and Nervous Diseases

摘　　要：目的探讨apelin对鼠脑缺血-再灌注后的保护作用及机制。方法改良线栓法制备CD-1小鼠脑缺血-再灌注模型。实验1:实验动物随机分为假手术(Sham)组、溶剂对照(Vehicle)组、缺血-再灌注(I/R)组、apelin-13小剂量(APLN-L)组、apelin-13中剂量(APLN-M)组及apelin-13大剂量(APLN-H)组;实验2:实验动物随机分为Sham组、Vehicle组、APLN-M组、APLN-M+PD98059(APLN+PD)组、PD98059+I/R(PD)组。再灌注后23h时,实验1检测各组神经功能评分、脑梗死体积、脑水肿、细胞凋亡及细胞外调节蛋白激酶(ERK1/2)的表达;实验2检测各组ERK1/2、Bax、Bcl-2、caspase-3的表达及cleaved caspase-3的活性。结果实验1:1APLN-H组神经功能评分明显低于Vehicle组(P<0.05);2梗死体积APLN-L、-M、-H组较Vehicle组减小;3脑组织含水量APLN-H、-M组明显低于Vehicle组(P<0.05);4TUNEL阳性细胞数APLN-H、-M组明显低于Vehicle组(P<0.05);5APLN-L、-M、-H组Bax、caspase-3、cleaved caspase-3表达明显低于Vehicle组(P<0.05);Bcl-2表达明显高于Vehicle组(P<0.05);6APLN-H、-M、-L组cleaved caspase-3活性明显低于Vehicle组(P<0.05);7 APLN-L、-M、-H组p-ERK1/2蛋白表达明显高于Vehicle组(P<0.05)。实验2:1APLN+PD组Bax、caspase-3、cleaved caspase-3表达明显高于APLN-M组,Bcl-2表达明显低于APLN-M组(P<0.05);2APLN+PD组cleaved caspase-3活性明显高于APLN-M组(P<0.05)。结论 Apelin-13对脑缺血-再灌注具有神经保护作用;ERK1/2信号通路参与了apelin-13的抗凋亡作用机制。Objective To study the protective effect of apelin on cerebral ischemia/reperfusion （ I/R） injury and the potential mechanism.Methods Focal transient cerebral ischemia was induced in male ICR mice using modified suture occlusion technique.In experiment 1, mice were randomly divided into 6 groups： sham group, vehicle group, I/R group, apelin-low dose （ APLN-L） group, apelin-middle dose （ APLN-M） group and apelinh-igh dose （ APLN-H） group.In experiment 2, mice were randomly divided into 5 groups： sham group, vehicle group, APLN-M group, APLN-M＋PD98059 （APLN＋PD） group and PD98059＋I/R （PD） group.Mice were reanesthetized and killed at 23 h after reperfusion.Neurological function, infarct volume, brain edema, apoptosis and ERK1/2 were measured in experiment 1.ERK1/2, Bax, Bcl-2 and caspase-3 were measured in experiment 2.Results Experiment 1： ①Neurological function scores were significant reduced in APLN-H group compared with vehicle group （ P〈0.05）; ②Apelin-13 treated mice demonstrated smaller infarct volumes compared with vehicle mice; ③Percentage of brain water content of APLN-H and-M groups decreased compared with vehicle group （ P〈0.05）;④Apoptotic cells decreased in APLN-H and-M groups compared with vehicle group （ P〈0.05）;⑤Bax, caspase-3 and cleaved caspase-3 were down-regulated and Bcl-2 was up-regulated in APLN-L,-M,-H groups compared with vehicle group （P〈0.05）; ⑥Cleaved caspase-3 activity was obviously lower in APLN-L, -M and -H groups than that in vehicle group （ P〈0.05 ）; ⑦P-ERK1/2 increased in APLN-L, -M, -H groups compared with vehicle group （ P〈0.05） .Experiment 2： ①Bax, caspase-3 and cleaved caspase-3 increased and Bcl-2 decreased in APLN＋PD group compared with APLN-M group （ P〈0.05 ）; ②Cleaved caspase-3 activity increased in APLN＋PD group compared with APLN-M group （P〈0.05）.Conclusion Apelin-13 protects the brain against ischemia/reperfusion injury.ERK1/2 signaling pathway is involved in the apel

关 键 词：APELIN-13 脑缺血-再灌注 神经保护 细胞外调节蛋白激酶 

分 类 号：R743-32[医药卫生—神经病学与精神病学]