摘要
目的探讨缺氧缺血性脑损伤时缺氧诱导因子1α(HIF-1α)表达及其与神经元凋亡的关系,推测HIF-1α在神经元凋亡中所起的作用。方法10日龄SD大鼠分为假手术组、单纯缺氧组和缺氧缺血组,在缺氧后4、8和24 h处死取脑。免疫组织化学方法检测HIF-1α、凋亡标志蛋白activated caspase-3的表达,TUNEL法检测凋亡细胞,HE染色观察脑组织病理改变。结果单纯缺氧组和缺氧缺血组HIF-1α的表达趋势相似,于缺氧后4 h升高,8 h达到高峰,24 h后下降。Activated caspase-3在两组中的表达趋势也相似,于缺氧后4 h、8 h有少量表达,24 h明显升高。TUNEL染色显示缺氧后随着时间的延长凋亡细胞数逐渐增多,24 h时明显增高。HE染色显示单纯缺氧和缺氧缺血组神经细胞有不同程度的损伤,24 h时细胞损伤程度重,细胞溶解缺失明显。对同一时间点的上述指标进行比较,单纯缺氧组HIF-1α表达高于缺氧缺血组(P<0.05),activated caspase-3表达、TUNEL阳性细胞及细胞损伤程度则低于缺氧缺血组(P<0.05)。结论缺氧缺血脑损伤时,HIF-1α表达与activated caspase-3表达趋势相反,HIF-1α表达量与损伤程度呈反相关关系。推测HIF-1α可能对神经元有保护作用。
Objective To investigate the re1αtionship between HIF-1α expression and neuron apoptosis in hypoxia/hypoxia ischemia brain injury and elucidate the role of HIF-1α in regu1αting neuron apoptosis. Methods Postnatal day 10 SD rats were divided into three groups ： the hypoxia ischemia group （HI）, the hypoxia group and sham controls. Rat brains were collected at 4 h, 8 h and 24 h after hypoxia from each group. Immunohistochemistry was used to detect the protein expression of HIF-1α and actived caspase-3. Apoptosis positive cells were determined by TUNEL staining. HE staining was used to detect histopathological damage. Results The expression of HIF-1α protein was significantly upregu1αted at 4 h, peaked at 8 h, and decreased at 24 h after hypoxia/HI. The expression level of HIF-1α protein in hypoxia/HI group was much higher than that in sham controls （P〈 0. 01）. The expression of activated caspase-3 protein was increased at 4 h and 8 h after hypoxia/HI and significantly upregu1αted at 24 h, but in sham controls the activated caspase-3 protein remains at a very low level （P〈 0. 01）. TUNEL staining showed that positive cells significantly increased at 24 h after hypoxia/HI. HE staining showed that neuronal degeneration and edema became prominent at 24 h after hypoxia/ HI. The expression of HIF-1α protein was higher in hypoxia groups than that in hypoxia ischemia groups at the same time points （P〈0.05）. However, the expression of activated caspase-3, the number of TUNEL positive ceils and the degree of histopathological damage were lower in hypoxia groups than that in hypoxia ischemia groups at the same time points （P〈0. 05）. Conclusions The variation tendency of HIF-1α and activated caspase-3 expression was opposite, and the expression of HIF-1α protein and histopathological damage degree was inverse corre1αtion in HIBD. Therefore, it suggested that HIF-1α may play a protective role in neuron after hypoxia/HI.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2008年第6期912-915,共4页
Journal of Sichuan University(Medical Sciences)
基金
国家自然科学基金(批准号30570623)
四川省科技厅应用基础项目(07JY029-067)
教育部留学回国人员启动资金(编号2006331-11-7)
四川大学华西医学中心CMB人力资源项目(编号00722)资助
