停通气缺氧预处理对脑出血模型大鼠缺氧诱导因子-1α的影响

首都医科大学学报 ›› 2006, Vol. 27 ›› Issue (5): 576-580.

停通气缺氧预处理对脑出血模型大鼠缺氧诱导因子-1α的影响

安立新¹, 王保国¹, 彭宇明¹, 袁芳², 孙梅珍²

1. 首都医科大学附属北京天坛医院麻醉科;2. 北京市神经外科研究所

收稿日期:2006-07-10 修回日期:1900-01-01 出版日期:2006-10-24 发布日期:2006-10-24
通讯作者: 王保国

Effects of Asphyxial Hypoxic Preconditioning on HIF-1α after Intracranial Hemorrhage in Rats

An Lixin¹, Wang Baoguo¹, Peng Yuming¹, Yuan Fang², Sun Meizhen²

1. Department of Anesthesiology, Beijing Tiantan Hospital, Capital University of Medical Sciences;2. Beijing Neurosurgery Institute, Capital University of Medical Sciences

Received:2006-07-10 Revised:1900-01-01 Online:2006-10-24 Published:2006-10-24

摘要/Abstract

摘要： 目的观察停通气缺氧预处理(HPC)对脑出血(ICH)模型大鼠神经行为学评分、血肿周围组织中缺氧诱导因子-1α(HIF-1α)的表达和一氧化氮(NO)含量、一氧化氮合酶(NOS)活性的影响.方法 180只雄性SD大鼠,体质量260～290 g,用数字表法随机分为假手术组(S组,60只)、脑出血组(I组,60只)和缺氧预处理组(P组,60只).所有大鼠麻醉后行气管插管并给予维库溴胺机械控制通气.P组进行停通气1 min、复通气5 min的缺氧预处理(反复4次),其他2组未做处理,仅进行机械通气.所有大鼠机械通气1 h后,拔出气管导管.采用立体定向技术,将50 Μl自体不凝血注入P组和I组动物的尾状核中,S组注入同样剂量的生理盐水.在ICH后6 h、24 h、48 h和72 h各时间点,从存活鼠中随机抽取10只大鼠记录神经行为学(NDS)评分和Rosenberg评分,其中5只连续切片进行HIF-1α免疫组化染色;另5只大鼠活杀后取脑,用分光光度法测定血肿周围组织中NO质量摩尔浓度和NOS酶活性.结果 P组神经行为学评分在ICH后 6 h、24 h和48 h均优于I组(P＜0.05).Rosenberg评分P组在6 h为3.9±1.5,优于I组的5.4±1.5(P＜0.01).P组和I组的HIF-1α阳性细胞明显增多,与S组相比差异有统计学意义(P＜0.01).P组在24 h HIF-1α阳性细胞数为(6.0±0.8)个,明显低于I组[(11.4±1.8)个,P＜0.01].NO质量摩尔浓度和NOS酶活力在ICH后也显著增加,其中P组NO质量摩尔浓度在24 h的变化明显轻于I组(P＜0.01).结论停通气缺氧预处理能够改善脑出血模型大鼠的神经功能预后,具有一定的脑保护作用.其机制可能与降低HIF-1α的表达,抑制脑组织中NO质量摩尔浓度和NOS酶活性增加有关.

关键词: 缺氧预处理, 脑出血, NDS评分, HIF-1α, NO, NOS

Abstract: Objective To investigate observe the effects of asphyxial hypoxic preconditioning on neurological symptoms,expression of Hypoxia-inducible factor-1α(HIF-1α),content of nitric oxide(NO) and nitric oxide synthase(NOS) in brain tissue after intracranial hemorrhage(ICH) in rats.Methods 180 male SD rats were randomly allocated into three groups: sham group(group S,n=60),ICH group(group I,n=60) and preconditioning group(group P,n=60).The rats were anesthetized,paralyzed with vecuronium 2 mg/kg and mechanically ventilated.The rats in P group were pretreated with four times of preconditioning,by being stopped ventilation for 1 min and reventilated for 5 min per circle.One hour later,endotracheal was extubated. ICH model was made by stereotactic injection of 50 μL antilogous blood into the caudate nucleus in group P and I,and 50 μL saline in group S.Neural deficit scores(NDS) and Rosenberg scores were evaluated and the expression of HIF-1α in cerebral tissues were detected by using immunohistochemistry techniques and the content of NO and NOS were assayed by spectrometry at 6 h,(24) h,48 h and 72 h after intracerebral hemorrhage.Results In group P,NDS scores were much better at 6 h,24 h and 48 h than that in group I(P<0.05).Rosenberg score was significantly decreased in group P at 6 h(3.9±1.5) as compared with group I(5.4±1.5,(P<)0.01).HIF-1α expression raised obviously at 24 h and increased to the 72 h after ICH.The number of HIF-1α positive cells was much higher in group I than that in group P at 24 h and 48 h after ICH(P<0.01).Compared with the S group,NO and NOS content in group P and I raised obviously after 6 h ICH.But in group P the changes of NO and NOS content were much less at(24) h than that in group I((P<)(0.01)).Conclusion Asphyxial hypoxic preconditioning improves NDS and Rosenberg scores and demonstrates cerebral protective effect after ICH in rats which maybe related to the decreasing of the HIF-1α expression and the depressing of the NO and NOS increase in brain tissue.

Key words: hypoxic preconditioning, intracerebral hemorrhage, NDS scores, HIF-1α, NO, NOS scores

中图分类号:

R743.34

安立新;王保国;彭宇明;袁芳;孙梅珍. 停通气缺氧预处理对脑出血模型大鼠缺氧诱导因子-1α的影响[J]. 首都医科大学学报, 2006, 27(5): 576-580.

An Lixin;Wang Baoguo;Peng Yuming;Yuan Fang;Sun Meizhen. Effects of Asphyxial Hypoxic Preconditioning on HIF-1α after Intracranial Hemorrhage in Rats[J]. Journal of Capital Medical University, 2006, 27(5): 576-580.

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