摘要
目的初步探讨液态氟碳(perfluorooctyl-bromide,PFOB)纳米粒对蛛网膜下腔出血后早期脑损的保护作用及其与低氧诱导因子1α(HIF-1α)的关系。方法健康雄性SD大鼠100只分为5个组:假手术组(Sham)、蛛血组(SAH)、蛛血+安慰剂组(SAH+vehicle)、蛛血+5 g/kg PFOB组(SAH+5 g/kg PFOB)和蛛血+10 g/kg PFOB组(SAH+10 g/kg PFOB),每组20只。采用颈内动脉穿刺法制作SAH模型。造模后24 h对每组大鼠进行神经行为功能缺损评分,检测脑含水量和血脑屏障(BBB)通透性,末端脱氧核苷酸介导的X-d UTP缺口末端标记法(TUNEL)检测神经元凋亡,免疫组化和Western blot检测HIF-1α蛋白表达情况。结果 PFOB纳米粒能够显著降低早期脑损伤,包括改善神经功能缺失、减轻脑水肿、降低血脑屏障通透性和减少神经元凋亡,且SAH+10 g/kg PFOB组降低效果明显高于SAH+5 g/kg PFOB组(P<0.05)。PFOB在降低早期脑损伤的同时能够显著抑制HIF-1α蛋白表达,且SAH+10 g/kg PFOB组抑制效果明显高于SAH+5 g/kg PFOB组(P<0.05)。结论液态氟碳纳米粒对蛛网膜下腔出血后早期脑损伤的保护作用可能与抑制HIF-1α蛋白表达有关。
Objective To determine the protective effect of perfluorooctyl-bromide（ PFOB）nanoparticles on the early brain injury（ EBI） in rats after subarachnoid hemorrhage（ SAH） and its relationship with hypoxia-inducible factor 1 alpha（ HIF-1α）. Methods A total of 100 healthy male Sprague Dawley rats were randomly divided into 5 groups,that is,sham-operation,SAH,SAH ＋ vehicle,SAH ＋5 mg/kg PFOB and SAH ＋ 10 mg/kg PFOB,with 20 animals in each group. Rat SAH model was established by endovascular perforation,and PFOB treatment（ injected through the caudal vein） was initiated in 1 h after SAH. After their neurobehavioral function was evaluated in 24 h after surgery,all rats were subsequently sacrificed to detect brain water content and the blood-brain barrier（ BBB） permeability. TUNEL staining was used to detect neural apoptosis,immunohistochemical assay and Western blotting to detect HIF-1α expression.Results PFOB treatment significantly alleviated EBI,including neurological dysfunction,brain edema,blood-brain barrier disruption and neural cell apoptosis,with the high-dose group more obvious（ P〈0. 05）.In addition,it also suppressed the expression of HIF-1α in the rat hippocampus. The effects of 10 g/kg PFOB were more obvious than those of 5 g/kg PFOB（ P〈0. 05）. Conclusion PFOB alleviates EBI after SAH,potentially through down-regulation of HIF-1α.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2016年第3期251-257,共7页
Journal of Third Military Medical University
基金
国家临床重点专科建设项目经费资助(财社[2011]170号)~~
关键词
蛛网膜下腔出血
早期脑损伤
液态氟碳纳米粒
低氧诱导因子1Α
subarachnoid hemorrhage
early brain injury
perfluorooctyl-bromide nanoparticles
hypoxia-inducible factor 1α
