(Pyr1)Apelin-13对布比卡因诱导停搏乳鼠心肌细胞PI3K/Akt通路的干预  

Intervention of(Pyr1)Apelin-13 on PI3K/Akt pathway in bupivacaine-induced neonatal rat cardiomyocyte arrest

作　　者：林婷婷[1] 陈超星 鲍娜娜[1] 施克俭[1] 董娇娇[1] 刘乐[1] LIN Tingting;CHEN Chaoxing;BAO Nana;SHI Kejian;DONG Jiaojiao;LIU Le(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》2024年第2期106-111,共6页Journal of Wenzhou Medical University

基　　金：国家自然科学基金项目(81900231,82200329);温州市基础性科研项目(Y2020769)。

摘　　要：目的:探讨Apelin/APJ系统在逆转布比卡因心肌毒性中的作用及机制。方法:提取乳鼠心肌细胞进行原代培养,随机分为4组:空白培养基组(DMSO组)、布比卡因1 mmol/L(Bup组)、(Pyr1)Apelin-132μmol/L组(Apl组)和布比卡因1 mmol/L+(Pyr1)Apelin-132μmol/L组(BAp组)。记录各组细胞基础自主搏动次数后,按照相应分组给药处理6 h。处理完毕后时间记为T0,记录T0至T12不同时间的细胞搏动次数;电镜下观察T12时心肌细胞线粒体形态;比色法检测T12时细胞培养液乳酸脱氢酶(LDH)含量;ELISA检测T12时心肌细胞中Apelin-13浓度;Western blot检测T12时心肌细胞中APJ、PI3K、Akt、p-PI3K、p-Akt蛋白的表达。结果:T0时Bup组全部心肌细胞停止搏动。与DMSO组比较,Bup组细胞搏动次数显著减少(P<0.05),线粒体肿胀空泡化,培养液LDH含量明显上升(P<0.05),心肌细胞中Apelin-13、APJ、p-PI3K和p-Akt蛋白表达均下调(P<0.05)。与Bup组比较,BAp组细胞搏动次数显著增加(P<0.05),线粒体结构明显改善,培养液LDH含量明显下降(P<0.05),心肌细胞中Apelin-13,APJ、p-PI3K和p-Akt蛋白表达均上调(P<0.05)。结论:(Pyr1)Apelin-13可逆转布比卡因诱导的心肌细胞停搏,机制也许与激活PI3K/Akt蛋白磷酸化有关。Objective:To explore the role and mechanism of Apelin/APJ system in myocardial toxicity of bupivacaine.Methods:Myocardial cells were extracted from neonatal mice for primary culture.The cells were randomly divided into four groups:blank medium group(DMSO group),bupivacaine 1 mmol/L group(Bup group),(Pyr1)Apelin-132μmol/L group(Apl group)and bupivacaine 1 mmol/L+(Pyr1)Apelin-132μmol/L group(BAp group).After the number of cell basal spontaneous beats were recorded in each group,the drug was administered according to the corresponding group for 6 h.The time after treatment was recorded as T0.The number of cell beats from T0 to T12 was recorded;the morphology of mitochondria in cardiomyocytes of T12 was observed by electron microscope;the content of LHD in cell culture medium by colorimetry;the concentration of Apelin-13 in cardiomyocytes of T12 was detected by ELISA.To detect the expression of APJ,PI3K,Akt,p-PI3K and p-Akt protein in cardiomyocytes of T12 was detected by Western blot.Results:All cardiomyocytes in Bup group stopped beating at T0.Compared with DMSO group,the number of cell beats was significantly decreased(P<0.05);mitochondria were swollen and vacuolated;the content of LDH in culture medium was significantly increased(P<0.05)and the expressions of Apelin-13,APJ,p-PI3K and p-Akt in cardiomyocytes were down-regulated(P<0.05)in Bup group.Compared with Bup group,the number of cell beats was significantly increased(P<0.05);the mitochondrial structure was obviously improved;the content of LDH in culture medium was significantly decreased(P<0.05)and the expression of Apelin-13,APJ,p-PI3K and p-Akt in cardiomyocytes was up-regulated(P<0.05)in BAp group.Conclusion:(Pyr1)Apelin-13 can reverse bupivacaine-induced cardiomyocyte arrest,which may be related to the activation of PI3K/Akt protein phosphorylation.

关 键 词：(Pyr1)Apelin-13 布比卡因 心肌细胞 PI3K/AKT通路 

分 类 号：R614.1[医药卫生—麻醉学]