一氧化氮合酶抑制药对大鼠弥漫性脑损伤后海马齿状回神经发生的影响  

Effects of NOS inhibitor on dentate gyrus neurogenesis after diffuse brain injury in adult rats

作　　者：孙莉莎[1] 徐江平[1] 

机构地区：[1]第一军医大学药理学教研室,广州510515

出　　处：《中南药学》2004年第1期17-20,共4页Central South Pharmacy

摘　　要：目的 观察一氧化氮合酶(NOS)抑制药对成年大鼠弥漫性脑损伤后海马齿状回神经发生的影响。方法 选用成年弥漫性脑损伤(DBI)大鼠模型,采用BrdU标记分裂细胞及免疫组织化学方法比较弥漫性脑损伤后2、4、6、8、12 d时一氧化氮合酶抑制药干预组大鼠与相应对照组大鼠之间海马齿状回神经前体细胞的增殖速度。结果成年大鼠弥漫性脑损伤后应用7-硝基引唑(7-NI)进行干预,明显抑制了脑损伤后不同时间点齿状回神经前体细胞增殖(P<0.01),以损伤后4 d时抑制作用相对更为明显。应用氨基胍(AG)进行干预也明显减少了大鼠弥漫性脑损伤后不同时间点齿状回BrdU免疫阳性细胞数目(P<0.01),以8 d时抑制作用相对最为明显。结论 NOS可能是弥漫性脑损伤后成年大鼠海马齿状回神经发生过程中一个重要的调节因子,不同类型的NOS在弥漫性脑损伤后神经发生过程中的不同阶段可能扮演了不同的角色。OBJECTIVE To investigate the effects of selective nitric oxide synthase (NOS) inhibitors on dentate gyrus neurogenesis after diffuse brain injury (DBI) in adult rat brain. METHODS Adult male SD rats were subjected to DBI model. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we compared the proliferation rate of neural precursor cells in the dentate gyrus between the NOS inhibitor (7-nitroindazole and Aminoguanidine) group and the corresponding control group at various time after DBI. RESULTS Administration of i. p. 7-nitroindazole significantly reduced the number of BrdU labeled cells in the dentate gyrus of adult rats at various time after DBI (P<0. 01) with a prominent inhibition on the neural precursor cell proliferation on the 4th day. Aminoguanidine also significantly inhibited the proliferation rate of neural precursor cells in the dentate gyrus after DBI. but its obvious inhibition presented on the 8th day. CONCLUSIONS The activation of NOS after DBI may be an important accommodation factor for dentate gyrus neurogenesis in adult rats. The NO coming of nNOS was probably involved in the early enhanced neurogenesis after DBI, while the NO originating from iNOS probably participated in the late enhanced neurogenesis primarily.

关 键 词：弥漫性脑损伤 一氧化氮合酶 神经发生 齿状回 

分 类 号：R96[医药卫生—药理学]