一氧化氮合酶在大鼠脑缺血再灌注损伤后时间-量的变化
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R743

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北京市科委资助项目;北京市教委科研项目


Time-amount Deviation of the Nitric Oxide Synthase in Cerebral Ischemic Reperfusion
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    摘要:

    目的探讨在大鼠可逆性大脑中动脉栓塞模型(MCAO)中,在不同的再灌注时间点NOS各亚型酶的发生发展规律。方法雄性SD大鼠用异氟烷吸入性麻醉,MCAO90 min后再灌注。分别在再灌注1,2,6,9,12,24 h后检测左、右侧大脑组织中NOS各亚型酶的活力(cNOS和iNOS),进行神经功能评分,取脑,切片,用TTC染色,经图像分析仪分析脑梗死灶体积。结果大脑中动脉栓塞导致了严重的脑缺血,再灌注激活了NOS的活性,使得cNOS和iNOS的活力在再灌注后的各个时间点都大幅度增加,至少持续到再灌注24 h。cNOS的高峰出现在再灌注后6h,iNOS的高峰出现在再灌注后9 h。梗死灶体积的增加与NOS活力的增加呈平行状态。结论原生型酶(cNOS)包括eNOS和nNOS,在缺血再灌注早期被诱导表达,其活力在再灌注6 h后达到高峰。iNOS,在正常生理状态下很少表达,其高峰出现在缺血后再灌9 h。cNOS和iNOS在缺血性脑损伤再灌注阶段发挥着重要的作用。

    Abstract:

    Objective To investigate the development and kinesis of NOS isoforms in different reperfusion time in a model of reversible middle cerebral artery occlusion(MCAO) in rats.Methods Male Sprague-Dawley rats were anesthetized with isoflurane and subjected to an intraluminal MCAO for 90 minutes and reperfusion thereafter.The activity of the different isoforms of NOS(cNOS and iNOS) from the right and left hemispheres was measured at 1,2,6,9,12,and 24 hours reperfusion respectively.Following neurological deficit evaluation,brains were removed and sectioned at different reperfusion time point respectively.The infarct volume was determined with an imaging analysis on the brain sections stained with TTC.Results Conditions of severe MCAO induced ischemia and reperfusion excessively activate NOS,resulting in activities of cNOS and iNOS were significantly increased in the ischemic hemisphere at all time points of reperfusion for 24 h. The peak activity of cNOS was at 6h after reperfusion while that of iNOS appeared at 9 h.The infarct volume was increased parallel to the increasing of NOS.Conclusion cNOS from endothelial cells(eNOS) and neurons(nNOS) is constitutively expressed enzymes,whose activity is stimulated by early ischemic and reperfusion injury and get peak activity in the brain at 6 h after reperfusion iNOS,which is very little present in healthy tissue,is induced shortly after ischemia but its peak activity appeared at 9 hours after reperfusion.Both cNOS and iNOS contribute to secondary late-phase ischemic damage.

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刘巍,王晶晶,闫明,吴琼,卢静,乔欣,焦守恕,王钜.一氧化氮合酶在大鼠脑缺血再灌注损伤后时间-量的变化[J].中国比较医学杂志,2007,(9):539~543,560.

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  • 最后修改日期:2007-07-05
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