Apelin-13对鼠脑缺血-再灌注后的作用及机制

Apelin-13对鼠脑缺血-再灌注后的作用及机制
杨燚;崔海瑛;祝春华;张聪;苗江永
【期刊名称】《脑与神经疾病杂志》
【年(卷),期】2015(000)006
【摘要】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&nbsp;injury.ERK1/2 signaling pathway is involved in the apelin-13 ’ s anti-apoptosis effect in cerebral ischemia/reperfusion.%
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）；⑦APLN-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。

【总页数】8页(P401-408)
【作者】杨燚;崔海瑛;祝春华;张聪;苗江永
【作者单位】050000石家庄，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;050000石家庄，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;050000石家庄，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;050000石家庄，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;050000石家庄，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
【正文语种】中文
【中图分类】R743.32
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