海马缺血神经元反义c-fos寡核苷酸对bcl-2、bax蛋白表达的影响

目的 :了解即早基因 c- fos在海马缺血再灌注神经元损伤中的作用。方法 :以大鼠四血管闭塞建立全脑缺血再灌注实验动物模型 ,向一侧海马内注射反义 c- fos寡核苷酸 ( ODNs)以阻断受损神经元 FOS蛋白的表达。采用免疫组织化学方法 ,显示 c- fos对海马受损神经元 bcl- 2、bax蛋白表达的影响 ;用 H- E染色观察海马神经元的病理变化。结果 :海马在缺血 2 0 min,再灌注 2 4 h后 ,注射正义 ODNs、随意 ODNs及 PBS组海马 CA1、CA2 区bcl- 2、bax蛋白阳性表达较注射反义 c- fos ODNs组明显 ( P<0 .0 5 ) ;H- E染色显示注射反义 c- fos ODNs侧海马神经元形态大致正常 ;注射正义 ODNs、随意 ODNs、PBS侧海马区有较多神经元呈核浓缩、胞浆明显红染的缺血性改变。结论 :c- fos在脑缺血再灌注损伤中对神经元具有损害作用 ,而且可能对 bcl- 2基因家族有间接的调控作用

Effect of antisense c-fos oligonucleotide on ischemia neutrons' expression of bcl-2 and bax in the hippocampus

Objective: In order to identify the action of the immediately early genes(IEGs) in the neutron injury resulted from ischemia reperfusion of hippocampus. Methods: the whole brain ischemia reperfusion animal model was established, in which the rat's four main brain vasculars were blocked, and one of it's hippocampus was injected with the antisense c-fos oligonucleotide to inhibit the expression of the FOS protein. In addition ,immunohistochemical method was used to indicate the effect on the neutrons' expression of bcl-2 and bax with H-E stain indexing the changes in the hippocampus. Results: Intrahippocampal administration of antisense c-fos oligonucleotides into rat brain decreases levels of the proteins bax and bcl-2 in the CA 1, CA 2 regions of the ipsilateral hippocampus after 24 hours of reperfusion. H-E stain showed that the shape of neurons injected antisense ODNs were nearly normal, but those injected sense ODNs or random ODNs indicate ischemial change in some degree, such as nucleus condensing and red stain of cytosol. Conclusion: From the results we get the conclusion that c-fos is harmful to neurons in ischemia-reperfusion-injury and it may modulate the actions of the bcl-2 family indirectly.