Inducible nitric oxide synthase expression in human cerebral infarcts
Inducible nitric oxide synthase expression in human cerebral infarcts
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DOI：
10.1007/s004010050977
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发表时间：
1999-03-01
影响因子：
12.7
通讯作者：
Iadecola, C
中科院分区：
文献类型：
--
作者：
Forster, C;Clark, HB;Iadecola, C
诱导型或“免疫”型一氧化氮合酶(INOS)可在多种细胞类型中被炎性刺激诱导，并合成有毒数量的NO。在大鼠局灶性脑缺血模型中，iNOS表达于侵入受损脑组织和局部血管的中性粒细胞。对iNOS抑制剂和iNOS缺失型小鼠的研究表明，iNOS产生的NO有助于缺血性脑损伤。在目前的研究中，我们试图确定iNOS在缺血性中风后是否也在人脑中表达。对有急性脑梗塞神经病理证据的尸检脑进行免疫组织化学研究。INOS免疫反应见于缺血脑内的中性粒细胞和缺血区内的血管。INOS阳性细胞对硝基酪氨酸也呈免疫反应，反映了NO衍生的过氧亚硝酸盐和亚硝酸盐对蛋白质的硝化作用。梗死区外未检测到iNOS或硝基酪氨酸免疫反应。这些观察结果提供了证据，证明iNOS在缺血性脑梗塞后在人脑中表达，并支持iNOS抑制剂可能对人类缺血性中风的治疗有用的假设。
The inducible or "immunological" isoform of nitric oxide synthase (iNOS) is induced in many cell types by inflammatory stimuli and synthesizes toxic amounts of NO. In rodent models of focal cerebral ischemia, iNOS is expressed in neutrophils invading the injured brain and in local blood vessels. Studies with iNOS inhibitors and iNOS null mice indicate that NO produced by iNOS contributes to ischemic brain injury. In the present study, we sought to determine whether iNOS is also expressed in the human brain after ischemic stroke. Studies were conducted using immunohistochemistry on autopsy brains with neuropathological evidence of acute cerebral infarction. iNOS immunoreactivity was observed in neutrophils infiltrating the ischemic brain and in blood vessels within the ischemic territory. iNOS-positive cells also were immunoreactive for nitrotyrosine, reflecting protein nitration by NO-derived peroxynitrite and nitrites. iNOS or nitrotyrosine immunoreactivity was not detected outside the region of the infarct. These observations provide evidence that iNOS is expressed in the human brain after ischemic infarction and support the hypothesis that iNOS inhibitors may be useful in the treatment of ischemic stroke in humans.