本文選題：肢體缺血預處理　切入點：腦缺血耐受　出處：《河北醫(yī)科大學》2006年博士論文

【摘要】： 缺血性腦病是臨床上常見病、多發(fā)病之一,嚴重危害著人類的健康。特別是神經細胞對缺血性損害非常敏感,長時間的缺血打擊使得神經細胞大量死亡,難以再生,從而留下許多嚴重甚至是不可逆性的后遺癥。因此,調動機體的內源性保護機制,提高神經細胞對缺血性損害的抵抗力,使其在蒙受較嚴重的缺血狀態(tài)下減輕損傷,保持存活,保證恢復血液供應后這些神經細胞仍具有正常生理功能,是缺血性腦病治療上的一個重要策略。1990年,日本學者Kitagiwa等首先發(fā)現,預先給予沙土鼠輕微、短時、不致引起神經元死亡的腦缺血,可減輕再次損傷性缺血引起的CA1區(qū)神經元死亡,此種現象稱為腦缺血耐受(brain ischemic tolerance),提前給予的亞致死性腦缺血稱為腦缺血預處理(brain ischemic preconditioning)。但是,這種操作很難作為一種腦缺血前的預防措施進入臨床應用。近年來,隨著缺血預處理研究的深入,發(fā)現并確定了遠端缺血預處理(remote ischemic preconditioning)的保護作用。遠端缺血預處理是指預先對靶器官以外的組織或器官進行缺血預處理,使靶器官產生缺血耐受的現象。研究發(fā)現,肢體、小腸和腎臟等器官的短暫缺血對后續(xù)的缺血再灌注心肌能產生保護作用。我室趙紅崗等也證實,反復3次股動脈夾閉和開放的肢體缺血預處理(limb ischemic preconditioning, LIP)可減輕隨后即刻發(fā)生的腦缺血再灌注引起的大鼠海馬CA1區(qū)錐體神經元延遲性死亡和凋亡,首次證實了遠隔器官缺血預處理對腦的保護作用。但是,這種遠端預處理與傳統(tǒng)的腦缺血預處理是否存在相似的保護機制尚不清楚。 絲裂原活化蛋白激酶(Mitogen-activated protein kinase, MAPK)是細胞內重要的信號傳導系統(tǒng),參與細胞生長、發(fā)育、分化和凋亡等一系列生理病理過程。近年來,MAPK的家族之一p38 MAPK在缺血耐受誘導中的作用引起了廣泛關注。研究發(fā)現,p38MAPK在同一器官缺血預處理的保護機制中發(fā)揮重要作用。例如:大鼠心臟4次的缺血預處理可以明顯對抗后續(xù)30分鐘缺血造成的心肌損傷,而p38 MAPK抑制劑SB 203580能
[Abstract]:Ischemic encephalopathy is one of the most common diseases in clinic. It is a serious hazard to human health. Especially, the nerve cells are very sensitive to ischemic damage, and the long period of ischemic attack results in the death of a large number of nerve cells and it is difficult to regenerate. As a result, many serious and even irreversible sequelae have been left. Therefore, the endogenous protective mechanism of the body can be mobilized to increase the resistance of nerve cells to ischemic damage, so that they can reduce the damage and survive in a more severe state of ischemia. Ensuring that these neurons still have normal physiological functions after restoring blood supply is an important strategy in the treatment of ischemic encephalopathy. In 1990, Japanese scholar Kitagiwa et al. first found that gerbils were given a mild, short-term advance. Cerebral ischemia, which does not cause neuronal death, can reduce the neuron death in CA1 area caused by re-injury ischemia. This phenomenon is called cerebral ischemic tolerance brain ischemic tolerance, and sublethal cerebral ischemia given in advance is called brain ischemic preconditioning. It is difficult to apply this procedure as a preventive measure before cerebral ischemia. In recent years, with the development of ischemic preconditioning, The protective effect of remote ischemic preconditioning was found and determined. Remote ischemic preconditioning refers to the phenomenon of ischemic preconditioning of tissues or organs outside the target organ in advance to induce ischemic tolerance in the target organ. Transient ischemia of organs such as small intestine and kidney can protect the myocardium from subsequent ischemia and reperfusion. Zhao Honggang and others in my room have also confirmed that. Repeated occlusion of femoral artery and open limb ischemic preconditioning (lip) could reduce delayed death and apoptosis of pyramidal neurons in the CA1 area of hippocampus induced by subsequent cerebral ischemia-reperfusion in rats. The protective effect of remote organ ischemic preconditioning on the brain is confirmed for the first time. However, it is not clear whether there is a similar protective mechanism between the remote preconditioning and the traditional ischemic preconditioning. Mitogen-activated protein kinase (MAPK) is an important signal transduction system in cells involved in cell growth and development. In recent years, the role of p38 MAPK in the induction of ischemic tolerance has attracted wide attention. It has been found that p38 MAPK plays an important role in the protective mechanism of ischemic preconditioning in the same organ. For example, four times of ischemic preconditioning in the rat heart can significantly counteract myocardial damage caused by 30 minutes of ischemia. The p38 MAPK inhibitor SB 203580 can
【學位授予單位】：河北醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R363

【引證文獻】

相關碩士學位論文 前1條

1 黃朔;關于高壓氧預處理對大鼠局灶性腦缺血再灌注損傷保護作用的研究[D];吉林大學;2012年

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本文編號：1700636