大鼠慢性间歇性缺氧后c-fos的表达与神经细胞凋亡的关系

Expression of c-fos Protein and Neuron Apoptosis in Rats after Chronic Intermittent Hypoxia

目的观察凋亡相关基因c-fos在慢性间歇性缺氧(CIH)大鼠大脑皮质及海马区中的表达,探讨其与睡眠呼吸暂停综合征(SAS)脑部病变的关系。方法取健康雄性SD大鼠30只,随机分为3组,即对照组、CIH4周组和CIH8周组,每组10只。分别用原位末端标记法(TUNEL)和免疫组织化学方法 (MaxVisionTM一步法)检测大鼠脑组织中的凋亡细胞和c-fos蛋白,比较3组的神经细胞的凋亡及c-fos蛋白的表达变化情况。结果 c-fos表达阳性细胞及凋亡细胞主要分布在大脑皮质深层和海马区。CIH4周组的c-fos阳性细胞数(19.25±3.61)及凋亡细胞数(4.57±0.76)均比对照组明显增高(P<0.01);与其余两组比较,CIH8周组的c-fos阳性细胞数(28.65±5.26)及凋亡细胞数(7.29±0.79)也均比其余2组明显增高(P<0.01)。结论 CIH引起了c-fos蛋白的表达增强,并可诱导神经细胞凋亡;c-fos蛋白的表达可能与CIH后神经细胞凋亡有关。

Objective To investigate the expression of the apoptosis-related genes（c-fos） in brain tissues of rats with chronic intermittent hypoxia（CIH） and their role in the pathogenesis of sleep apnea syndrome（SAS）.Methods Thirty healthy male SD rats were randomly assigned to three groups： the control group（sham CIH,10 mice） and two CIH groups that were respectively exposed to intermittent hypoxia for 4 weeks（CIH4,10 mice） and 8 weeks（CIH8,10 mice）.The expression of c-fos proteins was examined by immunohistochemistry and the neuron apoptosis in cerebral cortex and hippocampus of the rats by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling（TUNEL） staining.The neuron apoptosis and the expression of c-fos protein were compared among three groups.Results The results showed that c-fos-positive cells and apoptotic cells were distributed mainly over the cortex and hippocampus.Compared with the control group,CIH4 group showed a significant increase in c-fos-positive cells（19.25±3.61） and apoptotic cells（4.57±0.76）.Compared with the other two groups,CIH8 group demonstrated a significantly higher number of c-fos-positive cells（28.65±5.26） and apoptotic cells（7.29±0.79）（F=237.38,321.98,P〈0.01）.Conclusion These results indicate that CIH can induce increased expression of c-fos protein and the apoptosis of neurocytes and that the expression of c-fos protein may be a factor for cells apoptosis.