摘要
目的探讨大鼠局灶性脑缺血再灌注后神经细胞一氧化氮合酶(NOS)的表达与神经细胞凋亡的关系及米帕明的保护作用。方法采用大脑中动脉内栓线阻断法(MCAO)造成局灶性脑缺血再灌注模型。用原位细胞凋亡检测方法观察神经细胞凋亡;用免疫组织化学方法检测大鼠神经细胞(nNOS、iNOS)的阳性表达的细胞数目。结果与假手术对照组比较,脑缺血再灌注2h后缺血侧神经细胞nNOS、iNOS表达升高,并出现神经细胞凋亡,随着再灌注时间的延长,神经细胞iNOS的表达明显增强,凋亡神经细胞数逐渐增多,至24h达高峰,但神经细胞nNOS的表达并未见明显增强。米帕明保护组神经细胞nNOS、iNOS的表达和凋亡神经细胞数明显低于缺血再灌组(P<0.01)。结论脑缺血再灌注后缺血侧神经细胞nNOS的表达增强,iNOS的表达显著升高,使NO的形成增加,这可能是介导脑缺血再灌注后神经细胞凋亡的机制之一。米帕明具有下调神经细胞nNOS、iNOS的表达,减少NO的生成,抑制细胞凋亡,减轻缺血再灌注对大鼠神经细胞损伤的作用。
Objective To explore the relationship between NOS expression and neuron apoptosis in rat after focal brain ischemic-reperfusion,and to study the protective effect of hnipramine（Imi）. Methods The method of reversible middle cerebral artery occlusion（MCAO） was used to establish the model of focal brain ischemia-reperfusion injury in rats. Immunnhistn-chemistry was used to detect the expression of neuronal nitric oxide synthase（nNOS） and inducihl eNOS（iNOS） in the brain,and image analysis was also used.The apoptosis of neurons observed with terminal deoxynueleotidyl tranferase mediated dUTP-flourescein nick end-labeling（TUNEL） assay. Results Compared with that of the control group,the expression of nNOS and iNOS in the ischemie side increased at 2h after brain ischemic-reperfusion and TUNEL-positive cells appeared in these regions.The expression of iNOS and the number of TUNEL-positive cells progressively increased with time and peaked at 24h after reperfusion, whereas the expression of nNOS had no significant change,The nNOS and iNOS expression and the neuron apoptnsis of the Imi group were significantly decreased comparedwith those of the IRgrnup（P〈0.01）. Conclusions The inerased expression of NOS and the increased amount of NO might be one of the mechanisms of neuron apoptosis after focal brain ischemic reperfusion. Imipramine（Imi） can significantly inhibit the apoptosis by means of inhibiting the expression of NOS and reducing the production of NO, thus alleviating the injury of isehemic reperfusion to the brain.
出处
《老年医学与保健》
CAS
2006年第4期221-224,共4页
Geriatrics & Health Care
基金
国家自然科学基金资助项目(编号:30400549)
关键词
脑缺血
再灌注损伤
一氧化氮合酶
细胞凋亡
丙咪嗪
Brain ischemia
Repro＇fusion injury
Nitric-oxide synthase
Apoptosis
Imipramine
