Apelin-13通过激活ERK1/2通路复苏布比卡因诱导的心脏停搏  

Apelin-13 rescues bupivacaine-induced cardiac arrest in rats by activating ERK1/2 pathway

作　　者：王石 何玉婷 陈郑洁 林婷婷[1] 王权光[1] 林丽娜[1] WANG Shi;HE Yuting;CHEN Zhengjie;LIN Tingting;WANG Quanguang;LIN Li’na(Department of Anesthesiology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]温州医科大学附属第一医院麻醉科,浙江温州325015

出　　处：《温州医科大学学报》2020年第6期444-448,共5页Journal of Wenzhou Medical University

基　　金：国家自然科学基金资助项目(81670219);温州市科技计划项目(2019Y0471)。

摘　　要：目的:探讨Apelin-13对布比卡因诱导大鼠心脏骤停中的复苏作用及作用机制。方法:选择35只雄性SD大鼠,随机分为3组:假手术组(Sham组,n=5)、布比卡因+0.9%氯化钠溶液组(A组,n=15)、布比卡因+Apelin-13组(B组,n=15)。大鼠麻醉后开放股动静脉,静脉推注布比卡因30 mg·kg^-1制备心脏停搏模型,之后A组静脉注射等量0.9%氯化钠溶液,B组立即给予150μg Apelin-13。心脏停搏记为0 min并开始实施心肺复苏,按压至自主循环恢复(ROSC)或至40 min放弃。存活者观察至ROSC后120 min后处死,留取心肌组织。记录大鼠复苏率、生存率、开始给布比卡因到心脏停搏时间(T0)、心肺复苏开始至出现第1个自主心跳的时间(Ts)和心肺复苏开始至ROSC的时间(Tr);监测各组大鼠收缩压(SBP)、心率(HR)、收缩压与心率乘积(RPP)、复跳后各时点RPP与基础值的比值(RPPh);Western blot检测心肌组织中APJ、ERK1/2、p-ERK1/2蛋白的表达;ELISA检测心肌组织Apelin-13浓度。结果:与Sham组比较,A组心肌组织Apelin-13、APJ和p-ERK1/2蛋白表达下调(P<0.05)。与A组比较,B组复苏成功率和生存率升高、Tr缩短(P<0.05);与A组比较,ROSC后20 min内B组HR明显升高,ROSC后10~20 min内RPP和RPPh升高(P<0.05);与A组比较,B组心肌组织Apelin-13、APJ和p-ERK1/2蛋白表达上调(P<0.05)。结论:Apelin-13可解救布比卡因诱导的大鼠心脏停搏,其机制也许与激活ERK1/2通路蛋白磷酸化有关。Objective:To explore the role and mechanism of Apelin-13 in bupivacaine-induced cardiac arrest in rats.Methods:Thirty-five male SD rats were randomly divided into three groups:sham operation group(Sham group,n=5),bupivacaine+saline group(A group,n=15),bupivacaine+Apelin(B group,n=15).Rat femoral artery and vein open,intravenous bolus of bupivacaine 30 mg·kg^-1 was injected to cause cardiac arrest.B group was immediately given 150μg of Apelin-13,and A group was injected intravenously with the same amount of normal saline.Cardiac arrest was recorded as zero and cardiopulmonary resuscitation(CPR)was started until ROSC(return of spontaneous circulation)or the end of a 40 min period.The survivors were sacrificed 120 minutes after ROSC observation,and myocardial tissue was retained.The rate of the recovery,the rate of survival,the time from initiation of bupivacaine to cardiac arrest(T0),the time from the start of CPR to the first spontaneous heartbeat(Ts),and the time from the start of CPR to ROSC(Tr)and hemodynamics were recorded.The expression of APJ,ERK1/2 and p-ERK1/2 protein in myocardial tissue was detected by Western blot and the concentration of Apelin-13 in myocardial tissue by ELISA.Results:The results showed that compared with the Sham group,the expression of Apelin-13,APJ,p-ERK1/2 protein were signally down-regulated(P<0.05)in the A group.Compared with the A group,the recovery rate and the survival rate were increased,Tr shortened,hemodynamics improved significantly after ROSC and the expressions of Apelin-13,APJ,p-ERK1/2 protein were signally up-regulated(P<0.05)in the B group.Conclusion:Apelin-13 can rescue bupivacaine-induced cardiac arrest in rats,and the mechanism may be related to activation of ERK1/2 pathway protein phosphorylation.

关 键 词：APELIN-13 布比卡因 心脏停搏 ERK1/2 

分 类 号：Q319.1[生物学—遗传学]