缺氧诱导因子-1α在大鼠蛛网膜下腔出血后早期脑损伤中的作用
发布时间：2018-12-18 10:50
【摘要】：目的 虽然缺氧诱导因子-la (hypoxia inducible factor-la, HIF-la)在缺血缺氧脑损伤中有大量研究,但是有关HIF-1α在蛛网膜下腔出血(subarachnoid hemorrhage, SAH)后早期脑损伤(early brain injury, EBI)中的作用仍不清楚,本研究旨在探讨HIF-1α在SAH后EBI中的作用及相关机制。 方法 采用改良血管内穿刺法制作SAH模型。60只雄性SD大鼠随机分成以下3组：SAH+2ME2组(SAH+2ME2组)；SAH+二甲亚砜组(SAH+vehicle组)；假手术+二甲亚砜组(sham+vehicle组)。手术后24h对各组大鼠血脑屏障通透性、脑组织含水量、细胞凋亡和皮层HIF-1α、BNIP3和血管内皮生长因子(vascular endothelial growth factor, VEGF)表达水平进行检测；应用荧光双标染色法检测表达HIF-la的细胞类型及其与细胞凋亡是否共同表达；同时对各组大鼠手术后24h神经功能评分及死亡率进行统计分析。 结果 与sham+vehicle组比较,SAH后大脑皮层HIF-1α、BNIP3和VEGF的表达明显增多,同时细胞凋亡、血脑屏障通透性、脑水肿及神经功能缺损明显加重(P0.05)；与SAH+vehicle组比较,2ME2干预后大脑皮层HIF-1α、BNIP3和VEGF的表达显著性降低,血脑屏障破坏和脑水肿明显减轻,同时神经功能得到改善(P0.05)；免疫荧光双标染色显示HIF-1α蛋白主要表达于神经元和TUNEL阳性的细胞核中。 结论 我们研究显示HIF-1α可能通过调控靶基因BNIP3和VEGF的表达分别诱导细胞凋亡和加重血脑屏障破坏和脑水肿,从而在SAH后早期脑损伤中发挥重要作用。2ME2可通过抑制HIF-1α,进而降低BNIP3和VEGF表达,进而减轻SAH后细胞凋亡、血脑屏障破坏和脑水肿,改善大鼠神经功能。
[Abstract]:Objective although hypoxia inducible factor (la (hypoxia inducible factor-la, HIF-la) has been studied extensively in ischemic and hypoxic brain injury, HIF-1 伪 is involved in the early brain injury of (early brain injury, after subarachnoid hemorrhage (subarachnoid hemorrhage, SAH). The role of HIF-1 伪 in EBI after SAH is still unclear. Methods 60 male SD rats were randomly divided into three groups: SAH 2ME2 group (SAH 2ME2 group,); SAH dimethyl sulfoxide group, (SAH vehicle group) and sham operation dimethyl sulfoxide group (sham vehicle group), and 60 male SD rats were randomly divided into three groups: SAH 2ME2 group (SAH 2ME2 group,); SAH dimethyl sulfoxide group, (SAH vehicle group) and sham operation dimethyl sulfoxide group (sham vehicle group). The permeability of blood-brain barrier, water content of brain tissue, apoptosis and the expression of HIF-1 伪, BNIP3 and Vascular endothelial growth factor (vascular endothelial growth factor, VEGF) in cortex were detected 24 hours after operation. The cell types of HIF-la expression and their coexpression with apoptosis were detected by fluorescence double labeling staining, and the neurological function score and mortality rate of each group were statistically analyzed 24 hours after operation. Results compared with sham vehicle group, the expression of HIF-1 伪, BNIP3 and VEGF in cerebral cortex after SAH was significantly increased, apoptosis, blood-brain barrier permeability, brain edema and neural function defect were significantly aggravated (P0.05). Compared with SAH vehicle group, the expression of HIF-1 伪, BNIP3 and VEGF in cerebral cortex after 2ME2 intervention was significantly decreased, the blood-brain barrier damage and brain edema were alleviated, and the nerve function was improved (P0.05). Double immunofluorescence staining showed that HIF-1 伪 protein was mainly expressed in neurons and TUNEL positive nuclei. Conclusion our results suggest that HIF-1 伪 may induce apoptosis and aggravate the damage of blood-brain barrier and brain edema by regulating the expression of target gene BNIP3 and VEGF, respectively. 2ME2 can inhibit the expression of HIF-1 伪, then decrease the expression of BNIP3 and VEGF, and then reduce the apoptosis of cells after SAH, the damage of blood-brain barrier and brain edema, and improve the neural function of rats.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R651.15;R743
本文编号：2385735
[Abstract]:Objective although hypoxia inducible factor (la (hypoxia inducible factor-la, HIF-la) has been studied extensively in ischemic and hypoxic brain injury, HIF-1 伪 is involved in the early brain injury of (early brain injury, after subarachnoid hemorrhage (subarachnoid hemorrhage, SAH). The role of HIF-1 伪 in EBI after SAH is still unclear. Methods 60 male SD rats were randomly divided into three groups: SAH 2ME2 group (SAH 2ME2 group,); SAH dimethyl sulfoxide group, (SAH vehicle group) and sham operation dimethyl sulfoxide group (sham vehicle group), and 60 male SD rats were randomly divided into three groups: SAH 2ME2 group (SAH 2ME2 group,); SAH dimethyl sulfoxide group, (SAH vehicle group) and sham operation dimethyl sulfoxide group (sham vehicle group). The permeability of blood-brain barrier, water content of brain tissue, apoptosis and the expression of HIF-1 伪, BNIP3 and Vascular endothelial growth factor (vascular endothelial growth factor, VEGF) in cortex were detected 24 hours after operation. The cell types of HIF-la expression and their coexpression with apoptosis were detected by fluorescence double labeling staining, and the neurological function score and mortality rate of each group were statistically analyzed 24 hours after operation. Results compared with sham vehicle group, the expression of HIF-1 伪, BNIP3 and VEGF in cerebral cortex after SAH was significantly increased, apoptosis, blood-brain barrier permeability, brain edema and neural function defect were significantly aggravated (P0.05). Compared with SAH vehicle group, the expression of HIF-1 伪, BNIP3 and VEGF in cerebral cortex after 2ME2 intervention was significantly decreased, the blood-brain barrier damage and brain edema were alleviated, and the nerve function was improved (P0.05). Double immunofluorescence staining showed that HIF-1 伪 protein was mainly expressed in neurons and TUNEL positive nuclei. Conclusion our results suggest that HIF-1 伪 may induce apoptosis and aggravate the damage of blood-brain barrier and brain edema by regulating the expression of target gene BNIP3 and VEGF, respectively. 2ME2 can inhibit the expression of HIF-1 伪, then decrease the expression of BNIP3 and VEGF, and then reduce the apoptosis of cells after SAH, the damage of blood-brain barrier and brain edema, and improve the neural function of rats.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R651.15;R743
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相关期刊论文 前2条
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2 李丽华;屈艺;毛萌;母得志;;新生鼠缺氧缺血性脑损伤缺氧诱导因子1α表达与神经元凋亡[J];中国修复重建外科杂志;2007年12期
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