大鼠肢体缺血再灌注后海马NMDA受体2B亚单位表达的变化

发布时间：2018-10-25 12:05

【摘要】：脑本身的缺血-再灌注(I-R)损伤是全球的研究热点,但外周器官I-R 对脑的影响一直未被重视。肢体I-R 是肢体挤压伤、断肢再植术等走向康复的必由转归过程,长时间、严重缺血的肢体再灌注后可引发多器官功能障碍综合症(MODS)。对其处置不当,可导致多器官功能衰竭(MOF)。MOF 是此类患者最严重的并发症,其死亡率占重症监护患者死亡率的30-40%。因此,探讨肢体I-R 引发多器官损伤的机制,一直是创伤外科及重症医学共同关注的重大课题。既往的研究多集中在肾、肺等脏器上,本课题组的研究则发现,大鼠肢体I-R 后其海马区锥体层神经元也呈现明显的病理改变。海马是与学习、记忆及免疫调节密切相关的中枢部位,其损伤可能是外周创伤导致记忆缺失及免疫功能低下的重要原因。因此,在救治缺血肢体的同时,如何加强对脑的保护是一个不容忽视的问题,而阐明肢体I-R 引发海马神经元损伤的机制,具有重要的理论意义和临床应用价值。在缺血后神经元损伤的机制中,NMDA 受体(NR)介导的兴奋毒性倍受关注。NR 有功能亚单位(NR1)和调节亚单位(NR2)两部分组成,NR2 有A、B、C、D 四种类型,不同类型NR2 与NR1 结合后赋予NR 不同的生理及药理学特性。资料显示,成年大鼠海马区主要分布有NR2A、B 两种类型,NR2B 是突触后致密体中最主要的酪氨酸磷酸化蛋白
[Abstract]:Ischemia-reperfusion (I-R) injury of the brain itself is a hot topic in the world, but the effects of the peripheral organs I-R on the brain have not been paid much attention to. Limb I-R is the recovery process of limb crush injury, replantation of severed limb and so on. Long time, severe ischemia can lead to multiple organ dysfunction syndrome (MODS).) after limb reperfusion. (MOF). MOF is the most serious complication in patients with multiple organ failure, whose mortality rate is 30-40% of the mortality rate in intensive care patients. Therefore, exploring the mechanism of multiple organ injury induced by limb I-R has been a major concern of trauma surgery and critical medicine. Previous studies have focused on the kidneys and lungs, but our team found that the hippocampal pyramidal neurons also showed obvious pathological changes after I-R. Hippocampus is a central site closely related to learning, memory and immune regulation, and its injury may be an important cause of memory loss and hypoimmunity caused by peripheral trauma. Therefore, while treating ischemic limbs, how to strengthen the protection of the brain is a problem that can not be ignored. It is of great theoretical significance and clinical application value to clarify the mechanism of hippocampal neuron injury induced by I-R of limbs. In the mechanism of neuronal injury after ischemia, the excitotoxicity mediated by NMDA receptor (NR) has attracted much attention. NR consists of functional subunits (NR1) and regulatory subunits (NR2), and NR2 has four types of NR2. Different types of NR2 combined with NR1 gave NR different physiological and pharmacological characteristics. The data showed that there were two types of NR2A,B in hippocampus of adult rats, and NR2B was the most important tyrosine phosphorylation protein in postsynaptic compact body.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363

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