An S-nitrosylated hemoglobin derivative protects the rat hippocampus from ischemia-induced long-term potentiation impairment with a time window.
An S-nitrosylated hemoglobin derivative protects the rat hippocampus from ischemia-induced long-term potentiation impairment with a time window.
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DOI：
10.1254/jphs.fp0040385
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发表时间：
2004
影响因子：
3.5
通讯作者：
H. Otani;S. Jesmin;H. Togashi;I. Sakuma;K. Nakai;H. Satoh;M. Yoshioka;A. Kitabatake
中科院分区：
文献类型：
--
作者：
H. Otani;S. Jesmin;H. Togashi;I. Sakuma;K. Nakai;H. Satoh;M. Yoshioka;A. Kitabatake
有证据表明，s -亚硝基化是参与脑缺血的一个生物学过程。本研究的目的是阐明s -亚硝基化（SNO）聚乙二醇共轭（PEG）血红蛋白（Hb）作为一种人工氧载体，可以吸收游离NO并将NO转运到巯基（SH）部分，对缺血性脑功能障碍的影响。大鼠海马穿孔通路-齿状回突触的长期增强（LTP）作为短暂性脑缺血（2血管闭塞：2VO， 10 min）后4天的功能结果进行评估。SNO-PEG-Hb （250 mg/kg，静脉注射）在第0、1、2或4天（分别在再灌注后立即、24小时、48小时或96小时）减轻了2vo诱导的LTP损伤。当第1天或第2天给予SNO-PEG-Hb时，效果显著。SNO-PEG-Hb改变了2VO大鼠的NOS特征，在mRNA和蛋白水平上上调eNOS、nNOS和iNOS的表达；SNO-PEG-Hb进一步上调eNOS和nNOS表达，下调iNOS表达。这些发现提示SNO-PEG-Hb可能对大鼠海马缺血/再灌注引起的功能损伤具有保护作用，从而增加了作为人工氧载体在氧疗领域的应用潜力。
Evidence suggests that S-nitrosylation is a biological process involved in cerebral ischemia. The aim of the present study was to elucidate the effects of S-nitrosylated (SNO) polyethylene glycol-conjugated (PEG) hemoglobin (Hb) developed as an artificial oxygen carrier, which can absorb free NO and translocate NO to a sulfhydryl (SH) moiety, on ischemic cerebral dysfunction. Long-term potentiation (LTP) in the perforant path-dentate gyrus synapses of the rat hippocampus was evaluated as functional outcome 4 days after transient incomplete cerebral ischemia (2-vessel occlusion: 2VO, 10 min). SNO-PEG-Hb (250 mg/kg, i.v.) administered on Day 0, 1, 2, or 4 (immediately, 24 h, 48 h, or 96 h after reperfusion, respectively) alleviated 2VO-induced LTP impairment with a therapeutic time window. The effect was significant when SNO-PEG-Hb was administered on Day 1 or 2. SNO-PEG-Hb altered NOS features observed in the vehicle-treated 2VO rat, upregulation of eNOS, nNOS, and iNOS expressions at mRNA and protein levels; SNO-PEG-Hb further upregulated eNOS and nNOS and downregulated iNOS expressions. These findings suggest that SNO-PEG-Hb might have protective effects on the rat hippocampus from ischemia/reperfusion-induced functional damages, thereby increasing the therapeutic potential as an artificial oxygen carrier for use in the area of oxygen therapy.