一氧化氮合酶在脑缺血再灌注中的双重作用

目的 探讨短暂脑缺血再灌注后大鼠脑内3型一氧化氮合酶(nitric oxide synthase，NOS)的表达及作用，为脑缺血治疗提供理论依据。方法 采用免疫组织化学方法，用3型NOS的多克隆抗体检测大鼠局灶性脑缺血2h再灌注15min及22h NOS在脑内的表达情况。结果 大鼠脑缺血2h再灌注15min，在脑缺血边缘区的血管壁及神经细胞出现内皮型一氧化氮合酶(endothelial nitric oxide synthase，eNOS)上调表达；脑缺血2h再灌注22h，在脑梗死区内表达神经元型一氧化氮合酶(neuronal mitric oxide synthase，nNOS)的神经细胞减少，并出现表达诱导型一氧化氮合酶(inducible nitric oxide synthase，iNOS)的胶质细胞，同时梗死边缘区血管及神经细胞出现eNOS及iNOS的上调表达。结论 在短暂脑缺血再灌注早期，缺血区周围可能有eNOS相关的保护机制；亚急性期eNOS及iNOS的保护及损伤机制并存；因此，在短暂脑缺血早期恢复灌注后予选择性iNOS抑制剂及促进eNOS活性有可能减少迟发性神经损伤。

The Double Role of Nitric Oxide Synthase in Reperfusion Following Focal Cerebral Ischemia

Objective To study the expression of three isoforms of nitric oxide synthase (NOS) after transient cerebral ischemia-reperfusion in rat, and provide theoreticalbasisfortherapy.Methods In a model of reversible middle cerebral artery occlusion through monofilament nylon suture, by three isoforms of NOS polyclone antibody-SP immunochemisty technique, the expression of neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) after ischemia 2 h plus reperfusion 15 min and ischemia 2 h plus reperfusion for 22 h were detected. Results (1) 15 min reperfusion following 2 h ischemia, eNOS immunoreactivity in blood vesselsandneuronsattheborder of ischemic territory was upregulated. (2) 22 h reperfusion following 2 h ischemia, theexpressionofnNOSwasdownregulated within the infracted region and iNOS immunoreactivity were observed in glial cells infiltrating the infracted region.eNOSand iNOS immunoreactivitywereupregu- lated in blood vessels and neurons at the border of infarcted region. Conclusions The upregulated expression of eNOS in the early phase of reperfusion following transient ischemia may play a protective role at the border of ischemic territory;In the later phase of reperfusion the neuroprotective role of eNOS and the neurodegenetive role of iNOS are coexisting. So itsupportthehypothesisthattheselectiveiNOSinhibitors and/or eNOS enhancer may be useful to reduce the delayed cerebral ischemic injury.