摘要
目的:探讨新生大鼠缺氧/缺血性脑损伤时皮层神经元缺氧诱导因子-1α(HIF-1α)的表达及其与凋亡相关基因P53、Bcl-2的关系。方法:新生7日龄SD大鼠随机分为假手术组、单纯缺氧组和缺氧/缺血组,在缺氧或缺氧/缺血后3、6、12、24、72 h断头取脑,HE染色观察脑组织病理学改变,免疫组织化学方法检测皮层神经元HIF-1α、P53及Bcl-2表达情况。结果:单纯缺氧组和缺氧/缺血组大鼠脑组织HE染色显示:脑皮层神经元均有不同程度的损伤,于24 h时损伤最重,细胞溶解缺失明显;皮层HIF-1α于缺氧/缺血后3 h表达升高,12 h达高峰,之后呈下降趋势;皮层P53表达高峰较HIF-1α推后,24 h达高峰,之后呈下降趋势;Bcl-2表达规律与HIF-1α一致。假手术组P53/Bcl-2值约等于1;单纯缺氧组和缺氧/缺血组3、6、12 h 3个时间点上P53/Bcl-2值小于1,24、72 h 2个时间点上P53/Bcl-2值大于1。结论:在新生大鼠缺氧/缺血性脑损伤时,HIF-1α参与了对P53及Bcl-2的调控,在缺氧损伤早期可能具有抗凋亡作用。
Objective： To investigate the expression of HIF-la and explore the relationship between expression HIF-la and apoptosis related genes P53, Bcl-2 in hypoxia ischemia brain damage in neonatal rats. Methods： Post- natal day 7 SD rats were divided into three groups： sham group, the hypoxia group and the hypoxia-ischemia group. Rats＇ brain tissue were collected at 3, 6, 12, 24, 72 h after hypoxia or hypoxia-ischemia from each group. The histopathological damage was detected by HE staining. Immunohistochemistry was used to detect the expression of HIF-1 a, P53 and Bcl-2. Results： HE staining showed that neuronal degeneration and edema became prominent at 24 h in both hypoxia group and hypoxia-ischemia group. The expression of HIF-1 a protein was significantly up- regulated at 3 h, peak at 12 h, and then decreased in both hypoxia and hypoxia-ischemia group. The expression ofP53 protein was upregulated at 3 h, peak at 24 h, and then decreased in both hypoxia and hypoxia-ischemia group. The expression of Bcl-2 protein was similar with HIF-l a in hypoxia and hypoxia-ischemia group. The ratio of P53 and Bcl-2 was almost 1 in sham group, less than 1 at 3 h, 6 h,12 h, and more than 1 at 24 h and 72 h in both hy- poxia and hypoxia-ischemia groups. Conclusion： The HIF-1 a participates in the regulation of P53 and Bcl-2 in hypoxia ischemia brain damage in neonatal rats. HIF-l a may have protective role in the onset of hypoxia.
出处
《东南大学学报（医学版）》
CAS
2011年第2期319-323,共5页
Journal of Southeast University(Medical Science Edition)
基金
江苏省中医管理局科技项目(LB09073)
