大鼠缺血再灌注损伤后皮层瘦素受体表达及ERK2、STAT3、NOS变化的研究

发布时间：2018-09-17 17:43

【摘要】：目的在遭遇急性缺血再灌注损伤时,脑组织将做出快速反应,这种反应可表现在功能、代谢及基因表达等多个水平,且大多具有代偿意义。在功能方面,当遭受短暂缺血后,脑细胞将出现短暂的功能丧失,即短暂性脑缺血发作。与此同时,脑细胞的代谢亦发生明显的改变。脑细胞中与糖酵解有关的酶(如PGK-1、GAPDH、LDH-A、醛缩酶、丙酮酸激酶)表达增加,脑细胞从有氧代谢供能为主转变为以葡萄糖无氧酵解供能为主的代谢方式。此外,脑细胞中的各种保护性蛋白质亦产生增多。上述变化对于脑细胞的保护、损伤修复可能具有重要意义。与其它生理、病理现象一样,脑缺血再灌注损伤的反应具有复杂的分子基础,而这种分子基础的主要方面即是基因表达的改变。一些学者发现,脑缺血再灌注损伤能快速诱导一组及早基因的表达。这些及早基因大多数属原癌基因家族(如c-fos、c-jun、c-myc、Jun-B、fos-B等)编码多种转录因子。缺血再灌注损伤脑细胞通过这些转录因子对多种下游基因表达的调控而实现对脑细胞中多种代谢、功能及修复活动的调节。其次,在遭受短暂性脑缺血再灌注后,脑细胞中多种抗氧化酶(如SOD、NOS等),热休克蛋白基因(HSP70、HSP25、泛素等),糖酵解酶基因(如PGK-1、GAPDH、LDH-A、醛缩酶、丙酮酸激酶),钙处理基因(如Ca~(2+)-ATP酶、低钙蛋白等),低氧诱导因子-1(HIF-1)基因以及生长因子基因(如VEGF、FGF-1、TGF-β_1等)均表达增多。基因表达的改变在脑缺血及再灌注损伤的保护中可能具有重要的意义,探讨脑缺血再灌注损伤时基因表达的变化,可能为脑缺血再灌注损伤的防治找到新的途径。肥胖基因(obsese,ob,也称瘦素基因)1994年被成功克隆。随后又发现了ob基因的表达产物瘦素。瘦素是炎症过程中的一种急性期反应物,前炎症性因子能影响瘦素合成。细胞学研究与动物实验已经证明瘦素在急性炎症过程中起重要作用,作为炎症介质网络中的一种因子,具有抑制炎症的作
[Abstract]:Objective to respond rapidly to acute ischemia-reperfusion injury, which can be expressed at several levels, such as function, metabolism and gene expression. And most of them have compensatory significance. In terms of function, the brain cells suffer transient loss of function after transient ischemia, that is, transient ischemic attack. At the same time, the metabolism of brain cells also changed significantly. The expression of glycolytic enzymes (such as PGK-1,GAPDH,LDH-A, aldolase, pyruvate kinase) in brain cells was increased. In addition, a variety of protective proteins in brain cells are also produced. These changes may play an important role in the protection and repair of brain cells. As with other physiological and pathological phenomena, the response to cerebral ischemia-reperfusion injury has a complex molecular basis, and the main aspect of this molecular basis is the change of gene expression. Some researchers have found that cerebral ischemia reperfusion injury can quickly induce a group of early gene expression. Most of these early genes belong to the proto-oncogene family (such as c-fos-c-junc, Jun-BFS-B, etc.), which encode a variety of transcription factors. Through the regulation of the expression of many downstream genes by these transcription factors, the cerebral cells of ischemia-reperfusion injury can regulate the metabolism, function and repair activities of the brain cells. Secondly, after transient cerebral ischemia and reperfusion, many antioxidant enzymes (such as SOD,NOS), heat shock protein gene (HSP70,HSP25, ubiquitin), glycolytic enzyme gene (such as PGK-1,GAPDH,LDH-A, aldolase, pyruvate kinase), calcium processing gene (such as Ca~ (2) -ATPase) in brain cells, The expression of hypoxia inducible factor 1 (HIF-1) gene and growth factor gene (such as VEGF,FGF-1,TGF- 尾 1) increased. The changes of gene expression may play an important role in the protection of cerebral ischemia and reperfusion injury. To explore the changes of gene expression during cerebral ischemia reperfusion injury may provide a new approach for the prevention and treatment of cerebral ischemia-reperfusion injury. The obesity gene (obsese,ob, also known as the leptin gene) was successfully cloned in 1994. Then the expression product of ob gene leptin was found. Leptin is an acute stage reaction in the process of inflammation. Preinflammatory factors can affect leptin synthesis. Cytological studies and animal experiments have shown that leptin plays an important role in the process of acute inflammation. As a factor in inflammatory network, leptin has been shown to inhibit inflammation.
【学位授予单位】：中国医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

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