The expression changes and role of hypoxia-inducible factor-1a in the early stage of hypoxic-ischemic brain damage in neonatal rats
10.3760/cma.j.issn.2095-428X.2017.17.011
- VernacularTitle:缺氧缺血性脑损伤新生大鼠早期缺氧诱导因子-1α表达的意义
- Author:
Yunxia ZHAO
1
;
Guohui NIU
;
Jun WANG
;
Huachun XIONG
;
Junying YUAN
;
Mingmei WANG
;
Ping LI
;
Jiaojiao HUANG
;
Shuang AN
;
Dengna ZHU
Author Information
1. 450052,郑州大学第三附属医院儿童康复科
- Keywords:
Hypoxic-ischemic brain damage;
Hypoxia-inducible factor1 α;
2-methoxyestradiol;
Rat,newborn
- From:
Chinese Journal of Applied Clinical Pediatrics
2017;32(17):1321-1325
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the expression of hypoxia-inducible factor-1a(HIF-1α) at mRNA and protein levels in the early stage of hypoxic-ischemic brain damage (HIBD) in neonatal rats and its role.Methods (1) Experiment 1:thirty-six postnatal 7-day SD rats were divided into Sham group (n =6) and model group (HIBD,n =30) according to the random table method,then the rats in the model group were divided into 5 subgroups according to the time of sacrifice after HIBD(6 h,12 h,24 h,48 h,72 h,n =6).The expression levels of HIF-1cα mRNA and protein were detected by quantitative Real-time PCR(qPCR) and Western blot,respectively.(2) Experiment 2:forty-five postnatal 7-day SD rats were randomized into 3 groups:Sham group (n =15),HIBD group (n =15) and 2-methoxyestradiol(2ME2) group(n =15).According to the experiment 1,at the time point of the highest expression levels of HIF-1 α mRNA and protein,rats were killed and the brains were collected.The location and expression of HIF-1 α protein were detected by immunofluorescence,histopathological changes of brain were observed by HE staining,brain water content was measured by dry-wet method,cell apoptosis was detected by nick end labeling(TUNEL) method.Results At the early stage of HIBD,the expression levels of HIF-1 α mRNA and protein increased at first and then decreased,and the mRNA expression level (3.38 ± 0.21) and protein expression level (2.81 ± 0.36) were the highest at 24 h after HIBD.In Sham group,HIF-1 α protein was mainly expressed in the cytoplasm,while in HIBD group it was mainly expressed in the nucleus.The number of HIF-1α staining positive cells,brain water content and apoptosis rate were significantly different among Sham group,HIBD group and 2ME2 group (all P ＜ 0.05),and which were significantly lower in 2ME2 group than those in HIBD group (all P ＜ 0.05),and the pathological changes were also less serious than those in HIBD group.Conclusions The mRNA and protein levels of HIF-1 α are the highest at 24 h after HIBD.Inhibiting the expression of HIF-1 α can ameliorate the brain damage of neonatal rats induced by hypoxia-ischemia.Therefore,it is hypothesized that HIF-1α may cause injury in the early stage of HIBD in neonatal rats.
