ERK信号通路在瑞芬太尼减轻失血性休克复苏大鼠脑组织的氧化应激损伤的作用  

Effect of ERK signaling pathway on oxidative stress injury in brain tissue of rats with hemorrhagic shock resuscitation in remifentanil

作　　者：夏洁 刘丽 陈燕 Xia Jie;Liu Li;Chen Yan(Department of Anesthesia,the Sichuan Friendship Hospital,Chengdu 610000,China)

机构地区：[1]四川友谊医院麻醉科,成都610072 [2]四川友谊医院神经外科

出　　处：《脑与神经疾病杂志》2020年第12期762-768,共7页Journal of Brain and Nervous Diseases

摘　　要：目的探讨细胞外调节蛋白激酶(ERK)信号通路在瑞芬太尼减轻失血性休克复苏大鼠脑组织的氧化应激损伤的作用。方法将96只成年雄性SD大鼠作为研究对象,随机分为假手术组、失血性休克复苏组、瑞芬太尼组以及瑞芬太尼+ERK信号通路抑制剂U0126组,每组24只。建立大鼠失血性休克复苏模型,其中假手术组仅行动脉和静脉穿刺置管,瑞芬太尼组造模后给予1.0μg·kg^-1·min^-1瑞芬太尼注射液,失血性休克复苏组注射等量生理盐水,瑞芬太尼+ERK信号通路抑制剂U0126组在瑞芬太尼组基础上静脉注射0.05mg·kg-1 U0126。分别于大鼠放血前10 min(T0)、放血完成即刻(T1)、放血完成后30 min(T2)、放血完成后1 h(T3)和血液回输完成即刻(T4)对大鼠乳酸含量进行测定,并记录心率和平均动脉压;于回输血液完成后24h测定大鼠脑梗死体积、大鼠海马caspase-3表达水平以及脑组织p-ERK1/2表达水平、氧自由基水平、丙二醛MDA以及硝基酪氨酸含量;采用TUNEL法检测各组大鼠脑细胞凋亡情况。结果与假手术组相比,其他三组HR、MAP在T1、T2、T3时刻下降,乳酸含量上升,脑梗死体积以及海马caspase-3表达水平均显著上升;脑组织氧自由基、硝基酪氨酸以及MDA表达水平均上升,p-ERK1/2呈阳性表达,大鼠脑组织细胞凋亡细胞数阳性率均增加,差异均有统计学意义(P<0.05);与失血性休克复苏组相比,瑞芬太尼组脑梗死体积以及海马caspase-3表达水平、大鼠脑组织氧自由基、硝基酪氨酸以及MDA表达水平均明显下降,但瑞芬太尼+U0126组上述指标相比瑞芬太尼组均明显上升(P<0.05),且其与失血性休克复苏组相比差异无统计学意义(P>0.05);瑞芬太尼组凋亡细胞数阳性率相比失血性休克复苏组明显下降,p-ERK1/2表达阳性率显著上升(P<0.05),瑞芬太尼+U0126组凋亡细胞数阳性率相比瑞芬太尼组明显上升(P<0.05),胞质胞核p-ERK1/2表达阳性率显著下调Objective To investigate the role of ERK signaling pathway in reducing oxidative stress in brain tissue of rats with hemorrhagic shock by remifentanil.Methods 96 adult male SD rats were randomly divided into sham operation group,hemorrhagic shock resuscitation group,remifentanil group and remifentanil+ERK signaling pathway inhibitor U0126 group,24 rats in each group.The rat’s hemorrhagic shock resuscitation model was established by withdrawing 40%of the total blood volume from the right common carotid artery of the rat and continuing to return blood for 30 minutes after 1 hour.The sham operation group only underwent arterial and venous catheterization.The remifentanil group was given 1.0μg·kg-1·min-1 remifentanil injection,and the hemorrhagic shock resuscitation group was injected with the same amount of normal saline.Remifentanil+ERKsignaling pathway inhibitor U0126 group was intravenously injected with 0.05 mg·kg-1 U0126 on the remifentanil group.Rat lactic acid content was determined 10 min before the bloodletting(T0),immediately after the completion of bloodletting(T1),30 min after the completion of bloodletting(T2),1 h after the completion of bloodletting(T3),and immediately after the blood transfusion was completed(T4),and the heart rate(HR)and mean arterial pressure(MAP)were recorded;In addition,the cerebral infarction volume,the expression of caspase-3 in rat hippocampus,the expression level of p-ERK1/2 in brain tissue,the level of oxygen free radicals,malondialdehyde MDA and nitrotyrosine were measured 24 h after the completion of blood transfusion.At the same time,the apoptosis of brain cells was detected by TUNEL method.Results Compared with the sham operation group,the other three groups of HR and MAP decreased at T1,T2,and T3,and the lactic acid content increased.The volume of cerebral infarction and the expression of caspase-3 in the hippocampus increased significantly.The expression levels of oxygen free radicals,nitrotyrosine and MDA in brain tissue increased,p-ERK1/2 was positive,and the po

关 键 词：瑞芬太尼 ERK信号通路 失血性休克复苏 脑组织 氧化应激损伤 

分 类 号：R459.7[医药卫生—急诊医学]