细胞外调节激酶抑制剂PD98059对大鼠心肺复苏后脑缺血再灌注损伤的改善作用及其机制  

Protective effect and mechanism of extracellular signal-regulated kinase inhibitor PD98059 on cerebral ischemia reperfusion injury rats after cardiopulmonary resuscitation

作　　者：黄京菊 李诺 韦永先 王文艳[3] 覃涛[1] 杨叶桂 HUANG Jingju;LI Nuo;WEI Yongxian;WANG Wenyan;QIN Tao;YANG Yegui(Department of Critical Care Medicine,The Second Affiliated Hospital of Guangxi Medical University,Nanning 530005,China;不详)

机构地区：[1]广西医科大学第二附属医院重症医学科,南宁530005 [2]广西医科大学第一临床医学院 [3]桂林医学院附属医院重症医学科

出　　处：《山东医药》2023年第5期15-18,共4页Shandong Medical Journal

基　　金：广西卫生健康委科研基金项目(Z20190977,Z20211533);广西自然科学基金项目(2018GXNSFBA281045);广西医疗卫生重点学科(2020031)。

摘　　要：目的通过观察细胞外调节激酶(ERK)抑制剂PD98059对大鼠心肺复苏(CPR)后脑缺血再灌注损伤的改善作用,探讨其机制是否与抑制ERK/Calpain-2/Caspase-12信号通路、降低内质网应激介导的细胞凋亡有关。方法将36只SD大鼠随机分为对照组、PD98059组、假手术组各12只。除假手术组外,各组均经食道交流电刺激诱导建立心跳骤停/心肺复苏模型。电刺激诱导心跳骤停6min后,PD98059组、对照组大鼠经静脉分别注射0.3mg/kg PD98059及等体积生理盐水,并启动常规心肺复苏;假手术组仅进行手术操作而不行电刺激诱导心跳骤停。记录大鼠CPR后自主循环恢复(ROSC)时间、ROSC后24h神经功能评分(NDS);Western blotting法检测ROSC后24 h大鼠脑皮质组织中内质网应激相关凋亡蛋白钙蛋白酶2(Calpain-2)、天冬氨酸蛋白水解酶12(Caspase-12)、cleaved Caspase-3表达。结果PD98059组ROSC后24h NDS高于对照组(P<0.05),两组ROSC时间比较差异无统计学意义。大鼠脑组织Calpain-2、Caspase-12、cleaved Caspase-3蛋白假手术组<PD98059组<对照组(P均<0.05)。结论ERK抑制剂PD98059可以通过抑制ERK/Calpain-2/Caspase-12信号通路降低内质网应激介导的细胞凋亡水平,从而改善CPR后大鼠脑缺血再灌注损伤。Objective To investigate whether the extracellular regulatory kinase(ERK)inhibitor PD98059 alleviates cerebral ischemia-reperfusion injury after cardiopulmonary resuscitation(CPR)in Sprague-Dawley(SD)rats via inhibiting ERK/Calpain-2/Caspase-12 signaling pathway to decrease the endoplasmic reticulum stress-mediated apoptosis.Methods Thirty-six rats were randomly divided into three groups:the sham operation group(n=12),the normal saline group(n=12),and the PD98059 group(n=12).CPR models were established in all groups except the sham operation group by ventricular stimulation using transesophageal alternating current.Six minutes after the onset of electrical induction,a dose of 0.3mg/kg or equivalent normal saline was given to rats of the PD98059 group or the normal saline group,respectively,via femoral vein,followed by traditional CPR.The rats of the sham operation group were only treated with pre-operation.The duration to return of spontaneous circulation(ROSC)and the neurologic deficit score(NDS)at 24h after ROSC were recorded.The expression levels of endoplasmic reticulum stress and apoptosis-related proteins(calpain-2,Caspase-12,and cleaved Caspase-3)in cerebral cortex were detected by Western blotting at 24 h after ROSC.Results Compared with the normal saline group,the NDS in the PD98059 group was significantly higher at 24h after ROSC(P<0.05),and the time to ROSC showed no statistical difference.The expression levels of calpain-2,Caspase-12,and cleaved Caspase-3 in the cerebral cortex tissues presented the trend that Sham group<PD98059 group<normal saline group(all P<0.05).Conclusion PD98059 reduced endoplasmic reticulum stress-mediated apoptosis and alleviates cerebral ischemia-reperfusion injury via inhibiting ERK/Calpain-2/Caspase-12 signaling pathway in rats after cardiopulmonary resuscitation.

关 键 词：细胞外信号调节激酶抑制剂 细胞外调节激酶 钙蛋白酶2 天冬氨酸蛋白水解酶 缺血再灌注损伤 心肺复苏术 

分 类 号：R331.1[医药卫生—人体生理学]