外源性脂肪因子-13对大鼠脑缺血再灌注损伤的影响  

Effect of exogenous apelin-13 on cerebral ischemia-reperfusion injury in rats

作　　者：张治[1] 王强[1] 魏海东[1] 周恒[1] 汪惠文[1] 李立亚[1] 钟海星[1] 王枫[1] 熊利泽[1] 

机构地区：[1]第四军医大学西京医院麻醉科,西安市710033

出　　处：《中华麻醉学杂志》2014年第3期366-369,共4页Chinese Journal of Anesthesiology

摘　　要：目的：评价外源性脂肪因子-13对大鼠脑缺血再灌注损伤的影响。方法 SPF级SD雄性大鼠58只，6～8周龄，体重250～320 g ，采用随机数字表法，将其分为7组：假手术组（S组，n＝10）、脑缺血再灌注组（I/R组，n＝10）、二甲基亚砜组（D组，n＝6）、1 nmol脂肪因子-13组（A1组，n＝6）、5 nmol脂肪因子-13组（A5组，n＝10）、5 nmol脂肪因子-13＋PI3K抑制剂LY294002组（A5＋LY组，n＝10）和10 nmol脂肪因子-13组（A10组，n＝6）。采用线栓法制备局灶性脑缺血再灌注损伤模型，A1组、A5组、A5＋LY组、A10组和D组于脑缺血前30 min侧脑室注射相应剂量的脂肪因子-13、脂肪因子-13＋LY29400210 nmol ，或等容量二甲基亚砜。于再灌注24、72 h时进行神经行为学评分（NBS评分），于再灌注24 h时处死大鼠，取脑组织，进行细胞凋亡计数，并测定磷酸化糖原合酶激酶-3β（pGSK-3β）表达。再灌注72 h时处死大鼠，确定脑梗死体积。结果与S组比较，I/R组各时点NBS评分降低，脑梗死体积增大，脑组织神经细胞凋亡计数升高，脑组织pGSK-3β表达上调（ P＜0.05或0.01）；与I/R组比较，A5组和A10组NBS评分升高，脑梗死体积减少，A5组脑组织神经细胞凋亡计数减少，脑组织pGSK-3β表达上调（ P＜0.05）；与A5组比较，A5＋LY组NBS评分降低，脑梗死体积增大，脑组织pGSK-3β表达下调（ P＜0.05）。结论外源性脂肪因子-13可减轻大鼠脑缺血再灌注损伤，其机制与激活PI3K信号通路从而促进GSK-3β失活有关。Objective To evaluate the effect of exogenous apelin-13 on cerebral ischemia-reperfusion （I/R） injury in rats .Methods Fifty-eight male Sprague-Dawley rats ,aged 6-8 weeks ,weighing 250-320 g ,were randomly divided into 7 groups using a random number table ：sham operation group （group S , n=10 ） ,I/R group （n=10） ,dimethyl sulfoxide group （group D , n=6） ,apelin-13 （1 nmol） ＋ I/R group （group A1 , n=6） , apelin-13 （5 nmol ） ＋ I/R group （group A5 , n=10 ） ,apelin-13 （5 nmol ） ＋ LY294002 （PI3K inhibitor ） group （group A5 ＋LY , n=10） ,and apelin-13 （10 nmol） ＋ I/R group （group A10 , n=6） .Focal cerebral ischemia was produced by introducing a nylon intraluminal suture into the cervical internal carotid artery and advancing it intracranially to block blood flow into the middle cerebral artery according to the method described by Longa et al . The corresponding dose of apelin-13 ,apelin-13＋ LY294002 10 nmol ,or the equal volume of dimethyl sulfoxide was injected into the lateral cerebral ventricle in each group at 30 min before cerebral ischemia .Neurological function was assessed and scored using neurologic behavior scores （NBSs） at 24 and 72 h of reperfusion .The rats were sacrificed at 24 h of reperfusion and brains removed for detection of cell apoptosis and expression of phosphorylated-glycogen synthase kinase 3 beta （pGSK-3β） .The rats were sacrificed at 72 h of reperfusion to measure the cerebral infarct size .Results Compared with S group ,NBSs at each time point were significantly＆nbsp;decreased ,the cerebral infarct size was enlarged ,the number of apoptotic neurons was increased ,and pGSK-3βexpression was up-regulated in group I/R （ P〈0.05 or 0.01） .Compared with I/R group ,NBSs were significantly increased ,and the cerebral infarct size was decreased in A 5 and A10 groups ,and the number of apoptotic neurons was reduced ,and pGSK-3βexpression was up-regulated in group A5 （ P〈0.05） .NBSs were significantly lower , the

关 键 词：再灌注损伤 脑 脂肪因子-13 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]