p38MAPK参与肢体缺血预处理诱导的大鼠脑缺血耐受及其机制初探

发布时间：2018-04-02 13:33

本文选题：肢体缺血预处理　切入点：脑缺血耐受　出处：《河北医科大学》2006年博士论文

【摘要】： 缺血性脑病是临床上常见病、多发病之一,严重危害着人类的健康。特别是神经细胞对缺血性损害非常敏感,长时间的缺血打击使得神经细胞大量死亡,难以再生,从而留下许多严重甚至是不可逆性的后遗症。因此,调动机体的内源性保护机制,提高神经细胞对缺血性损害的抵抗力,使其在蒙受较严重的缺血状态下减轻损伤,保持存活,保证恢复血液供应后这些神经细胞仍具有正常生理功能,是缺血性脑病治疗上的一个重要策略。1990年,日本学者Kitagiwa等首先发现,预先给予沙土鼠轻微、短时、不致引起神经元死亡的脑缺血,可减轻再次损伤性缺血引起的CA1区神经元死亡,此种现象称为脑缺血耐受(brain ischemic tolerance),提前给予的亚致死性脑缺血称为脑缺血预处理(brain ischemic preconditioning)。但是,这种操作很难作为一种脑缺血前的预防措施进入临床应用。近年来,随着缺血预处理研究的深入,发现并确定了远端缺血预处理(remote ischemic preconditioning)的保护作用。远端缺血预处理是指预先对靶器官以外的组织或器官进行缺血预处理,使靶器官产生缺血耐受的现象。研究发现,肢体、小肠和肾脏等器官的短暂缺血对后续的缺血再灌注心肌能产生保护作用。我室赵红岗等也证实,反复3次股动脉夹闭和开放的肢体缺血预处理(limb ischemic preconditioning, LIP)可减轻随后即刻发生的脑缺血再灌注引起的大鼠海马CA1区锥体神经元延迟性死亡和凋亡,首次证实了远隔器官缺血预处理对脑的保护作用。但是,这种远端预处理与传统的脑缺血预处理是否存在相似的保护机制尚不清楚。丝裂原活化蛋白激酶(Mitogen-activated protein kinase, MAPK)是细胞内重要的信号传导系统,参与细胞生长、发育、分化和凋亡等一系列生理病理过程。近年来,MAPK的家族之一p38 MAPK在缺血耐受诱导中的作用引起了广泛关注。研究发现,p38MAPK在同一器官缺血预处理的保护机制中发挥重要作用。例如:大鼠心脏4次的缺血预处理可以明显对抗后续30分钟缺血造成的心肌损伤,而p38 MAPK抑制剂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
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363

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