MEK/ERK/NRF2信号通路参与小鼠低温致心肌氧化应激损伤的机制研究  

Mechanism of mitogen-activated protein kinase kinase/extracellular signal regulated kinases/nuclear factor erythroid 2-relat⁃ed factor 2 signaling pathway involved in myocardial oxidative stress injury caused by hypothermia in mice

作　　者：游平飞 于新辉 戴晶 曹滨验 胡安 邵兵 金红旭 刘颖 YOU Ping-fei;YU Xin-hui;DAI Jing;CAO Bin-yan;HU An;SHAO Bing;JIN Hong-xu;LIU Ying(Department of Emergency Medicine,General Hospital of Northern Theater Command,Shenyang 110000,China)

机构地区：[1]北部战区总医院急诊医学科,辽宁沈阳110016 [2]北部战区总医院麻醉科,辽宁沈阳110016

出　　处：《创伤与急危重病医学》2024年第5期272-276,共5页Trauma and Critical Care Medicine

摘　　要：目的探讨重度意外性低体温对小鼠心肌的影响,并进一步明确丝裂原活化蛋白激酶/细胞外调节蛋白激酶/碱性亮氨酸拉链转录因子(MEK/ERK/NRF2)通路参与心肌氧化应激损伤的可能机制。方法将20只雄性C57BL/6健康小鼠随机分为对照组(n=10)和模型组(n=10)。对照组小鼠常规饲养,模型组小鼠低温环境饲养致心肌损伤。监测两组小鼠核心体温改变情况、检测小鼠心肌损伤标志物、观察两组小鼠心脏大体结构变化、试剂盒检测心脏活性氧水平、Western blot检测心肌组织MEK1、ERK1/2、NRF2、超氧化物歧化酶2(SOD2)、丙二醛-5(MDA-5)蛋白的表达及免疫组化验证MEK1、ERK1/2蛋白的表达。结果模型组小鼠核心体温低于对照组,肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)水平高于对照组,差异有统计学意义(P<0.05)。与对照组比较,模型组小鼠心脏大体标本可见出血点、水肿,其表面黯淡,颜色加深,部分边缘不整;部分心肌出现炎症细胞浸润,心肌纤维出现不规则、交错排列。模型组的活性氧水平高于对照组,MDA-5蛋白表达高于对照组,SOD2蛋白表达低于对照组,MEK1蛋白表达高于对照组,ERK1/2蛋白表达高于对照组,NRF2蛋白表达高于对照组,MEK1、ERK1/2的阳性区域面积比例高于对照组,差异有统计学意义(P<0.05)。结论重度意外性低体温可对小鼠心肌造成氧化应激损伤,该氧化应激损伤的发生机制可能与MEK/ERK/NRF2信号通路有关。Objective To explore the effects of severe accidental hypothermia on mouse myocardium and to further clarify the possible mechanisms of mitogen-activated protein kinase kinase/extracellular signal regulated kinases/nuclear factor erythroid 2-related factor 2(MEK/ERK/NRF2)pathway involved in myocardial oxidative stress injury.Methods Twenty male C57BL/6 healthy mice were randomly divided into control groups(n=10)and model groups(n=10).The mice in the control group were routinely reared,and the mice in the model group were reared in a low-temperature environment to cause myocardial injury.The success of the model was verified by monitoring the changes in core body temperature,detecting the markers of myocardial injury,observing the changes in the cardiac macrostructure and of the two groups of mice;and the success of the model was verified by the detection of cardiac reactive oxygen species level by the kit,and by the detection of the expression of MEK1,ERK1/2,NRF2,superoxide dismutase2(SOD2),and malondialdehyde-5(MDA-5)proteins in myocardial tissues by Western blot,and the verification of the immunohistochemistry.MEK1,ERK1/2 protein expression and immunohistochemical verification.Results The levels of creatine kinase(CK),creatine kinase myocardial band(CK-MB)and lactatedehydrogenase(LDH)in model groups were higher than those of the control group,with statistically significant differences(P<0.05).Compared with the control group,hemorrhagic spots and edema were seen in the macroscopic specimens of the heart of the mice in the model group,whose surfaces were dull and deepened in color,and some of the edges were uneven;some of the myocardium appeared to be infiltrated with inflammatory cells,and the myocardial fibers appeared to be irregularly and staggeredly arranged.In the model group,the ROS level was higher than that of the control group,the MDA-5 protein expression was higher than that of the control group,the SOD2 protein expression was lower than that of the control group,the MEK1 protein expression was higher

关 键 词：低温 心脏 氧化应激 丝裂原活化蛋白激酶 细胞外调节蛋白激酶 碱性亮氨酸拉链转录因子 

分 类 号：R542.2[医药卫生—心血管疾病]