【摘要】 目的:研究慢性脑血流低灌注对脑组织中一氧化氮(nitric oxide,NO)生成的影响,以及S-腺苷甲硫氨酸(S-adenosylmethionine,SAM)对NO生成的干预作用。方法:采用双侧颈总动脉结扎(two-vesselocclusion,2-VO)大鼠模型模拟慢性脑血流低灌注过程,并给予SAM干预治疗。采用western blot方法检测大鼠脑皮层诱导型一氧化氮合成酶(inducible nitric oxide synthase,i NOS)的表达,用Griess反应检测NO的含量,用免疫组织化学方法观察胶质细胞的形态学改变。结果:慢性脑血流低灌注早期星形胶质细胞及小胶质细胞激活,i NOS及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达增高;在脑血流低灌注慢性期,星形胶质细胞及小胶质细胞的激活减少,TNF-α含量下降,然而i NOS表达持续增高,同时伴有NO含量增高。SAM干预可抑制慢性脑血流低灌注诱导的i NOS的高表达,减少NO的含量。结论:SAM可以通过抑制NO产生在脑血流低灌注引发的晚期氧化应激损伤中发挥神经保护作用。更多还原

【Abstract】 Objective To investigate the production of nitric oxide(NO) in rat brain under chronic cerebral hypoperfusion and the protective effect of S-adenosylmethionine(SAM) on inhibiting NO production. Methods Two-vessel occlusion(2-VO) rat models were used; iNOS expression and NO production were tested by western blot and Griess reaction, respectively; the activation of glial cells were observed by immunohistochemistry. Results astrocytes and microglial cells were activated in the early stage of chronic cerebral hypoperfusion, and the expression of iNOS and TNF-α were increased. While, in thechronic stage, the activation of astrocytes and microglial cells, as well as the level of TNF-α were reduced. However, the expression of iNOS was continuously increased, accompanied with the high production of NO. SAM could reverse the up-regulation of NO and iNOS level induced by chronic cerebral hypoperfusion. Conclusion SAM could play a neuroprotective role by inhibiting the production of NO in late oxidative stress injury induced by chronic cerebral hypoperfusion.更多还原