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Journal of ZheJiang University(Medical Science)  2014, Vol. 43 Issue (1): 58-65    DOI: 10.3785/j.issn.1008-9292.2014.01.009
    
The relationship between hypoxia-inducible factor-1α expression and apoptosis in early brain injury after subarachnoid hemorrhage
HU Qiang,WU Cheng,CHEN Jing-yin,YAN Feng,LI Jian-ru,CHEN Gao
Department of Neurosurgery, Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China
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Abstract  

Objective: To investigate the association of hypoxia-inducible factor-1α (HIF-1α) expression and apoptosis in the cerebral cortex following subarachnoid hemorrhage (SAH).
Methods: Subarachnoid hemorrhage was induced by modified monofilament puncture method in rats.Thirty-five adult male Sprague-Dawley rats were randomly assigned to five groups: sham-operated group,SAH 6 h,SAH 12 h,SAH 24 h and SAH 72 h groups.HIF-1α expression was assessed by immunofluorescence staining.TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique was adopted to detect apoptotic cells.Double immunolabeling was used to identify cell types with positive HIF-1α expression.
Results: The expression of HIF-1α was increased at 6 h (4.65%±1.01%),peaked at 24 h (18.55%±4.23%),and decreased at 72 h (6.31%±1.15%) after SAH (P<0.05).TUNEL-positive cells were up-regulated in the brain at 6 h (7.09%±2.34%),peaked at 24 h (25.54%±7.36%),and down-regulated at 72 h (14.11%±3.03%) after SAH (P<0.05).A significant positive correlation was noted between HIF-1α positive rates and TUNEL positive rates following SAH (r=0.738,P<0.05).Double immunolabeling indicated that HIF-1α was expressed predominantly in neurons and some nuclei with positive HIF-1α were co-stained with TUNEL.
Conclusion: The data indicate that HIF-1α might participate in the pathological progression of early brain injury after SAH.



Key wordsSubarachnoid hemorrhage      Hypoxia-inducible factor 1      alpha subunit/metabolism      Brain injuries      Apoptosis      Statistics(as topic)      Rats      Sprague-Dawley      Disease models      animal      Random allocation     
Received: 24 July 2013      Published: 04 January 2014
Cite this article:

HU Qiang,WU Cheng,CHEN Jing-yin,YAN Feng,LI Jian-ru,CHEN Gao . The relationship between hypoxia-inducible factor-1α expression and apoptosis in early brain injury after subarachnoid hemorrhage. Journal of ZheJiang University(Medical Science), 2014, 43(1): 58-65.

URL:

http://www.zjujournals.com/xueshu/med/10.3785/j.issn.1008-9292.2014.01.009     OR     http://www.zjujournals.com/xueshu/med/Y2014/V43/I1/58


蛛网膜下腔出血大鼠早期大脑皮层低氧诱导因子-1α表达与细胞凋亡相关性研究

目的:研究大鼠蛛网膜下腔出血(SAH)后大脑皮层低氧诱导因子-1α (HIF-1α) 的表达情况及其与细胞凋亡可能存在的关系,初步探讨HIF-1α表达在SAH后早期脑损伤中的作用。
方法:采用改良血管内穿刺法建立SAH模型。35只成年雄性SD大鼠随机分入假手术组和SAH 6、12、24、72 h组。采用免疫荧光染色技术检测HIF-1α的表达水平,末端脱氧核苷酸介导的X-dUTP缺口末端标记法(TUNEL)检测细胞凋亡,同时应用免疫荧光双标染色技术检测表达HIF-1α的细胞类型。
结果:免疫荧光染色结果显示HIF-1α的表达在假手术组几乎未见(0.29%±0.30%),SAH后6 h增加(4.65%±1.01%),24 h达高峰(18.55%±4.23%),差异均有统计学意义(均P<0.05)。TUNEL法检测到大鼠大脑凋亡细胞数在SAH后增多,6 h时可见少数凋亡细胞(7.09%±2.34%),在24 h到达高峰(25.54%±7.36%),差异有统计学意义(P<0.05)。相关分析显示各组HIF-1α阳性率与TUNEL阳性率呈正相关(r=0.738,P<0.05)。免疫荧光双标染色显示HIF-1α蛋白主要表达于神经元,部分HIF-1α染色阳性的细胞核与TUNEL染色重合。
结论:大鼠SAH后早期脑损伤过程中HIF-1α表达与细胞凋亡呈正相关,提示HIF-1α可能参与SAH后早期脑损伤病理生理过程。


关键词: 蛛网膜下腔出血,  缺氧诱导因子1,  α亚基/代谢,  脑损伤,  细胞凋亡,  统计学(主题),  大鼠,  Sprague-Dawley,  疾病模型,  动物,  随机分配 
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