缺血后处理通过mdm2-p53负反馈通路减轻大鼠缺血再灌注损伤后的氧化应激反应  

Ischemic post-conditioning attenuates oxidative stress after ischemia-reperfusion injury by inducing activation of the mdm2-p53 negative signaling loop in rats

作　　者：李晓倩[1] 陈凤收[1] 张再莉[1] 马虹[1] LI Xiao-qian;CHEN Feng-shou;ZHANG Zai-li;MA Hong(Department of Anesthesiology,the First Hospital of China Medical University .Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院麻醉科

出　　处：《实用药物与临床》2019年第9期916-920,共5页Practical Pharmacy and Clinical Remedies

基　　金：国家自然科学基金(81601053);辽宁省教育厅科学技术研究项目(LK201636)

摘　　要：目的观察和探讨缺血后处理(Ischemic post-conditioning,IPC)对大鼠脊髓缺血再灌注损伤(Spinal cord ischemia reperfusion injury,SCIRI)后氧化应激反应的影响及机制。方法 60只SD大鼠随机分为3组:假手术组(Sham组)、缺血再灌注组(IR组)和缺血后处理组(IPC组)。Sham组:仅暴露主动脉弓不夹闭;IR组:直视下主动脉弓夹闭14 min后去除动脉夹以模拟SCIRI;IPC组:SCIRI损伤,于再灌注5 min后给予5个循环缺血后处理。SCIRI后48 h内每12 h采用BBB法评价大鼠后肢运动和反射功能;取L4-6节段脊髓测定组织中MDA和SOD的含量;Western blot法测定脊髓组织中p53和mdm2的蛋白含量。结果与Sham组比较,IR组大鼠BBB评分降低,后肢运动和反射能力明显下降;与IR组比较,IPC组上述指标有明显改善(P<0.05)。与Sham组比较,IR组大鼠MDA明显升高,SOD明显下降;与IR组比较,IPC组MDA明显下降,SOD明显升高(P<0.05)。与Sham组比较,IR组大鼠mdm2明显下降,MDA明显升高;与IR组比较,IPC组mdm2明显升高,p53明显下降(P<0.05)。上述变化在术后24 h变化最为显著。结论缺血后处理通过激活脊髓组织中mdm2-p53负反馈通路,增加脊髓组织中SOD含量、减少MDA含量,从而发挥抗氧化应激的神经保护作用。Objective To observe and investigate the effect and mechanisms of ischemic post-conditioning(IPC)on regulating oxidative stress after spinal cord ischemia reperfusion injury(SCIRI)in rats.Methods Totally 60 SD rats were divided into three groups:Sham group,IR group and IPC group.Sham group:only exposed the aortic arch without clamping;IR group:clamped on aortic arch for 14 min,then removed the arterial clip to mimic SCIRI in rats;IPC group:performed 5 cycles of ischemic post-conditioning after 5 min post-IR.The hind-limb motor and reflex function were evaluated by BBB method at a 12 h-interval during 48 h post-IR.At the same time,L4-6 segment of spinal cords was collected to determine the MDA and SOD contents;the protein levels of p53 and mdm2 was determined using Western blot.Results Compared with Sham group,the BBB scores in IR group were significantly decreased and there was obviously impaired hind-limb motor and reflex ability.Compared with IR group,the above indexes were greatly improved in IPC group(P<0.05).Compared with Sham group,the significantly increased MDA content and decreased SOD content were observed in IR group.Compared with IR group,the significantly decreased MDA content and increased SOD content were observed in IPC group(P<0.05).Compared with Sham group,the significantly increased MDA and decreased mdm2 protein level were observed in IR group.Compared with IR group,the significantly decreased p53 protein level and increased mdm2 protein level were observed in IPC group(P<0.05).All these changes were the most significant at 24 h after operation.Conclusion Ischemic post-conditioning is capable to activate the mdm2-p53 negative signaling loop in injured spinal cords,which results in the increased SOD content and decreased MDA content,thereby exhibiting neuroprotections against oxidative stress.

关 键 词：缺血后处理 脊髓缺血-再灌注损伤 MDM2-P53 丙二醛 超氧化物歧化酶 

分 类 号：R651.2[医药卫生—外科学]