PD98059抑制内质网应激和改善心肺复苏大鼠脑损伤  

PD98059 Inhibits Endoplasmic Reticulum Stress and Improves Brain Damage in Rats with Cardiopulmonary Resuscitation

作　　者：张宗祥 谢露[2] 李诺[1] 郑君慧[1] 杨叶桂 陈蒙华[1] ZHANG Zong-xiang;XIE Lu;LI Nuo;ZHENG Jun-hui;YANG Ye-gui;CHEN Meng-hua(The Second Hospital Affiliated to GuangxiMedical University,Nanning 5300072;Department of Physiology,School of Pre-Clinical Sciences,Guangxi Medical University,Nanning)

机构地区：[1]广西医科大学第二附属医院,530007 [2]广西医科大学基础医学院

出　　处：《岭南急诊医学杂志》2020年第2期133-135,共3页Lingnan Journal of Emergency Medicine

基　　金：国家自然科学基金项目(81160231,81660312)。

摘　　要：目的:探究大鼠心脏骤停/心肺复苏(Cardiac arrest/Cardiopulmonary resuscitation,CA/CPR)后全脑缺血再灌注损伤中,ERK抑制剂PD98059(PD)是否影响内质网应激(endoplasmic reticulum stress,ERS)而起到脑保护作用的。方法:采用经食道交流电刺激的方法诱导大鼠发生心脏骤停、制备CA/CPR后全脑缺血再灌注损伤模型,将恢复自主循环(ROSC)的大鼠随机分为PD组、模型组(CA组)、DMSO组,每组6只,分别经静脉给予PD(0.3 mg/kg)、等量生理盐水及等量5%DMSO。另外随机选取6只健康大鼠为假手术组(Sham组),行手术操作而不诱导CA/CPR。在ROSC或手术操作完成24小时后进行神经功能评分并取脑,在经Western blot检测脑皮质中内质网应激相关蛋白:免疫球蛋白结合蛋白(immunoglobulin-binding protein,BIP)、C/EBP同源蛋白(CHOP)的表达量。结果:CA组、DMSO组及PD组ROSC24小时神经功能评分比Sham组明显下降[(66.17±2.04),(65.33±2.16),(74.67±1.63)vs(79.50±0.84),P<0.05],PD组ROSC24小时神经功能评分明显高于CA组和DMSO组(P<0.05);,CA组和DMSO组的BIP、CHOP的表达量明显高于Sham组(P<0.05);PD组的BIP、CHOP的表达量明显低于CA组和DMSO组(P<0.05)。结论:PD对大鼠心脏骤停/心肺复苏后的全脑缺血再灌注损伤有保护作用,其机制可能是通过抑制ERK后减轻内质网应激,下调促凋亡因子CHOP表达发挥作用。Objective:To explore whether ERK inhibitor PD98059(PD)can protect the brain by influencing endoplasmic reticulum stress(ERS)in rats with global cerebral ischemia-reperfusion injury injury after cardiac arrest/cardiopulmonary resuscitation(CA/CPR).Methods:we used transesophageal AC stimulation to induce cardiac arrest in rat and establish the model of global cerebral ischemia-reperfusion injury after CA/CPR.Once rats recovered of spontaneous circulation(ROSC),were randomly divided into four groups:PD group(Intravenous injection PD 0.3 mg/kg,n=6),model group(CA group,injection equal amount of normal saline,n=6),and DMSO group(injection equal amount of 5%DMSO,n=6).In addition,we randomly selected 6 healthy rats as sham operation group(sham group),and only operated without inducing CA/CPR.Then perform neurological function scores on rats after the completion of ROSC or surgical procedures 24 hours,and take out the brain tissue.At the same time,the expression of immunoglobulin binding protein(BIP),C/EBP homologous protein(CHOP)were detected byWestern blot.Results:At 24 after ROSC,the neurological function scores of CA group,DMSO group and PD group were significantly lower than the Sham group[(66.17±2.04),(65.33±2.16),(74.67±1.63)vs(79.50±0.84),P<0.05].The neurological score of PD group was higher than that of CA group and DMSO group(P<0.05).The expression of BIP,chop in CA group and DMSO group were significantly higher than that in sham group(P<0.05).However,the expression of BIP,chop in PD group were significantly lower than that in CA group and DMSO group(P<0.05).Conclusion:PD has protective effect on global cerebral ischemia-reperfusion injury after cardiac arrest/cardiopulmonary resuscitation in rats.Its mechanism may be to reduce ERS and down regulate the expression of apoptotic factor chop after inhibiting ERK.

关 键 词：PD98059(PD) 心肺复苏(CPR) 缺血再灌注损伤(IRI) 内质网应激(ERS) 

分 类 号：R459.7[医药卫生—急诊医学]