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大鼠缺血再灌注損傷后皮層瘦素受體表達及ERK2、STAT3、NOS變化的研究

發(fā)布時間:2018-09-17 17:43
【摘要】:目的 在遭遇急性缺血再灌注損傷時,腦組織將做出快速反應(yīng),這種反應(yīng)可表現(xiàn)在功能、代謝及基因表達等多個水平,且大多具有代償意義。在功能方面,當(dāng)遭受短暫缺血后,腦細胞將出現(xiàn)短暫的功能喪失,即短暫性腦缺血發(fā)作。與此同時,腦細胞的代謝亦發(fā)生明顯的改變。腦細胞中與糖酵解有關(guān)的酶(如PGK-1、GAPDH、LDH-A、醛縮酶、丙酮酸激酶)表達增加,腦細胞從有氧代謝供能為主轉(zhuǎn)變?yōu)橐云咸烟菬o氧酵解供能為主的代謝方式。此外,腦細胞中的各種保護性蛋白質(zhì)亦產(chǎn)生增多。上述變化對于腦細胞的保護、損傷修復(fù)可能具有重要意義。與其它生理、病理現(xiàn)象一樣,腦缺血再灌注損傷的反應(yīng)具有復(fù)雜的分子基礎(chǔ),而這種分子基礎(chǔ)的主要方面即是基因表達的改變。一些學(xué)者發(fā)現(xiàn),腦缺血再灌注損傷能快速誘導(dǎo)一組及早基因的表達。這些及早基因大多數(shù)屬原癌基因家族(如c-fos、c-jun、c-myc、Jun-B、fos-B等)編碼多種轉(zhuǎn)錄因子。缺血再灌注損傷腦細胞通過這些轉(zhuǎn)錄因子對多種下游基因表達的調(diào)控而實現(xiàn)對腦細胞中多種代謝、功能及修復(fù)活動的調(diào)節(jié)。其次,在遭受短暫性腦缺血再灌注后,腦細胞中多種抗氧化酶(如SOD、NOS等),熱休克蛋白基因(HSP70、HSP25、泛素等),糖酵解酶基因(如PGK-1、GAPDH、LDH-A、醛縮酶、丙酮酸激酶),鈣處理基因(如Ca~(2+)-ATP酶、低鈣蛋白等),低氧誘導(dǎo)因子-1(HIF-1)基因以及生長因子基因(如VEGF、FGF-1、TGF-β_1等)均表達增多;虮磉_的改變在腦缺血及再灌注損傷的保護中可能具有重要的意義,探討腦缺血再灌注損傷時基因表達的變化,可能為腦缺血再灌注損傷的防治找到新的途徑。 肥胖基因(obsese,ob,也稱瘦素基因)1994年被成功克隆。隨后又發(fā)現(xiàn)了ob基因的表達產(chǎn)物瘦素。瘦素是炎癥過程中的一種急性期反應(yīng)物,前炎癥性因子能影響瘦素合成。細胞學(xué)研究與動物實驗已經(jīng)證明瘦素在急性炎癥過程中起重要作用,作為炎癥介質(zhì)網(wǎng)絡(luò)中的一種因子,具有抑制炎癥的作
[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.
【學(xué)位授予單位】:中國醫(yī)科大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2005
【分類號】:R363

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