1400W对成年大鼠脑缺血后海马神经元再生的影响  

Effect of 1400W on neurogenesis after transient focal cerebral ischemia in the adult rat hippocampus

作　　者：王玮[1] 孙勇军[1] 奚涛[2] 朱东亚[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]中国药科大学生物制药学院,南京210009

出　　处：《中国药理学通报》2004年第1期33-37,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题 No 3 9670 85 6;国家科技部生命科学中心<国家重点科技攻关计划>课题 No 96 90 1 0 5 2 0 5

摘　　要：目的　研究脑缺血对海马齿状回神经元再生的刺激作用 ,以及iNOS抑制剂对缺血诱发的神经元再生的影响。方法　血管内栓线法阻塞大脑中动脉 1 5h然后再灌注制备再灌性局灶脑缺血模型。腹腔注射iNOS抑制剂 14 0 0W(5mg·kg-1)。BrdU参入法测定海马齿状回的细胞扩增。于再灌注后 2 4h测定海马iNOS活性及NO水平。结果　在脑缺血后d 8缺血侧海马齿状回的BrdU阳性细胞数比对照侧多大约 5倍 ,14 0 0W抑制iNOS活性和降低NO水平 ,同时抑制脑缺血诱发的海马齿状回神经细胞扩增。结论　iNOS是脑缺血诱发海马齿状回神经元再生的重要分子 ,激活iNOS可能是促进脑缺血损伤功能修复的治疗策略之一。AIM To determine whether ischemia affects neurogenesis in dentate gyrus and whether ischemia induced neurogenesis is inhibited by iNOS inhibitor 1400W. METHODS The middle cerebral artery in rats was occluded for 1 5 h by an intraluminal filament and then reperfused to prepare transient focal cerebral ischemia. iNOS inhibitor 1400W (5 mg·kg -1 ) was injected intraperitoneally. A bromodeoxyuridine (BrdU) labeling method was used to identify the postproliferation cells in dentate gyrus. The measurement of iNOS activity and NOx concentration in the hippocampus were performed at 24 h after reperfusion. RESULTS The number of BrdU positive cells in the ipsilateral dentate gyrus increased about 5 fold 8 days after ischemia, compared with that in the contralateral. Inhibition of iNOS by 1400W prevented ischemia induced cells proliferation in the dentate gyrus. CONCLUSION Our results indicate that iNOS is necessary for ischemia stimulated cell birth in the dentate gyrus of adult rats and activation of iNOS may provide a possible strategy for functional recovery from cerebral ischemic insult.

关 键 词：1400w 诱生型一氧化氮合酶 神经元再生 脑缺血 

分 类 号：R-332[医药卫生] R322.81