丝裂原活化蛋白激酶在脑缺血损伤中的作用及其调控机制

Role of mitogen activated protein kinases in cerebral ischemic injury and the mechanism of modulation

目的:综述丝裂原活化蛋白激酶介导的信号转导在脑缺血损伤中的时空动态分布规律及其调控表达机制,为抑制脑缺血性神经元损伤和保护神经功能寻找新的途径。资料来源:应用计算机检索Medline1996-01/2005-11涉及丝裂原活化蛋白激酶与脑缺血损伤相关的文章,检索词“mitogenactivatedproteinkinase(MAPK)/function/activation/signaltransduction,cerebralischemia,neuronrehabilitation”,并限定文章语言种类为English。资料选择:对资料进行初审,纳入标准:选择与“丝裂原活化蛋白激酶生物学功能、活化、转导、脑缺血损伤、神经元修复”有关文章,并在1996年以后发表的文章,排除标准:重复性文章。资料提炼:共搜集到200篇相关文章,排除158篇。入选42篇用于综述,其中有关丝裂原蛋白激酶在脑缺血损伤活化的22篇,有关其在脑缺血损伤修复调控机制的20篇。资料综合:丝裂原活化蛋白激酶信号传导途径的各亚类通路在组织细胞缺血时均会发生相应的变化,可能参与细胞损伤或修复过程的调控,在神经元细胞死亡和存活中起重要作用,抑制其级联反应可改变动物模型的脑缺血损伤。结论:丝裂原蛋白激酶在脑缺血和再灌注损伤中反应性激活,并在神经损伤修复过程中起重要作用,因此对丝裂原活化蛋白激酶途径的调节可能是抑制脑缺血性神经元损伤和保护神经功能的新途径。

OBJECTIVE： To summarize the mechanism and the dynamic changes of mitogen activated protein kinases （MAPK） activation, so as to provide a new method to inhibit neuronal cell damage and neuroprotection in therapeutic aspect in ischeroic stroke. DATA SOURCES： A computer-based online search of Medline database was undertaken to identity articles about the correlation between MAPK and cerebral ishcemic injury published in English between January 1996 and November 2005, the keywords were ＂mitogen activated proteinkinase （MAPK）/function/activation/signal transduction, cerebral ischemia, neuron rehabilitation＂. STUDY SELECTION： All articles were selected firstly. Inclusive criteria： articles published after 1996 relevant to the biological function, activation and signal transduction of MAPK, cerebral ischemia and neuron repair. Exclusive criteria： duplicated articles. DATA EXTRACTION： Totally 200 articles were collected, and 158 were excluded, 42 were selected for review, including 22 about the activation of MAPK in cerebral ischemie injury, and 20 about its modulation in the repair of cerebral ischemic injury. DATA SYNTHESIS： The subsets of the signal transduction pathway of MAPK had corresponding ehanges at histocyte ischemia, and may be involved in the modulation of cellular injury or repair, and it plays an important role in the death and survival of neurons. The inhibition of its cascade reaction can change the cerebral ischemic injury of animal models. CONCLUSION： The MAPK signaling pathway responds actively in cerebral ischemia and reperfusion, which might act as an important survival signal in neuronal cell damage. So the modulation of the MAPK signaling pathway may serve as an inhibition in neuroprotection in therapeutic aspect in ischemic stroke.