Selective inhibition of inducible nitric oxide synthase prevents ischaemic brain injury
Selective inhibition of inducible nitric oxide synthase prevents ischaemic brain injury
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DOI：
10.1038/sj.bjp.0702549
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发表时间：
1999-05-01
影响因子：
7.3
通讯作者：
Plotkine, M
中科院分区：
文献类型：
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作者：
Parmentier, S;Böhme, GA;Plotkine, M
1本研究旨在探讨诱导型钙非依赖性一氧化氮合酶（inducible calcium-independent nitric oxide synthase，iNOS）抑制剂N-（3-（aminomethyl）benzyl）acetamidine（1400 W）对实验性大鼠局灶性脑缺血的功能和组织病理学的影响。在动脉闭塞后18 h开始给予1400 W（20 mg kg（-1））或溶剂，包括间隔8 h皮下注射7次。Isc血液结局和NOS活性（组成型和钙非依赖性NOS）进行了评估3天升降机缺血。3 1400 W显著减少缺血性病变体积31%，4 1400 W使梗死区钙非依赖性NOS活性降低36%而不影响组成型NOS活性。5这些发现表明iNOS激活有助于组织损伤，并且该同种型的选择性抑制剂可能对中风的治疗有意义。
1 The aim of this study was to investigate the effect of N-(3-(aminomethyl )benzyl)acetamidine (1400W), a selective inhibitor of inducible calcium-independent nitric oxide synthase (iNOS), on the functional and histopathological outcomes of experimental transient focal cerebral ischaemia in rats,2 Transient ischaemia was produced by the occlusion for 2 h of both the left middle cerebral artery and common carotid artery. Treatments with 1400W (20 mg kg(-1)) or vehicle were started 18 h after occlusion of the arteries and consisted in seven subcutaneous injections at 8 h interval. Isc haemic outcomes and NOS activities (constitutive and calcium-independent NOS) were evaluated 3 days Lifter ischaemia.3 1400W significantly reduced ischaemic lesion volume by 31%, and attenuated weight loss and neurological dysfunction.4 1400W attenuated the calcium-independent NOS activity in the infarct by 36% without affecting the constitutive NOS activity.5 These findings suggest that iNOS activation contributes to tissue damage and that selective inhibitors of this isoform may be of interest for the treatment of stroke.