缺氧预处理对大鼠脑出血后神经行为学评分和脑水含量的影响

Effects of asphyxial hypoxic preconditioning on the neurological symptoms and water content after intracranial hemorrhage in rats

目的:观察缺氧预处理对大鼠脑出血后死亡率、神经行为学评分、脑组织水含量的影响,进一步探讨缺氧预处理的脑保护作用。方法:实验于2004-11/2005-05在北京市神经外科研究所完成。140只雄性SD大鼠随机分为假手术组20只,脑出血对照组60只和缺氧预处理组60只。每组水合氯醛腹腔麻醉后行气管插管并给予肌松药维库溴胺(2mg/kg),机械控制通气。缺氧预处理组进行停通气1min、复通气5min的缺氧预处理反复4次。三组机械通气1h后,拔出气管导管。然后对缺氧预处理组和脑出血对照组采用立体定向技术,将50μL自体不凝血注入尾状核中制备脑出血模型,假手术组注入同样剂量的生理盐水。观察造模后1h内的循环情况,并于造模后6,24,48,72h进行神经行为学评分和姿势反射评分,计算死亡率。各组随机在上述各时间点取5只存活大鼠,麻醉处死后断头取脑,干湿重法测量不同脑区的含水量。结果:140只大鼠中,模型全部成功,非人为处死而自然死亡的动物32只,进入结果分析大鼠108只。进行神经功能评分和Rosenberg评分,脑组织水含量测定的大鼠60只。①假手术组20只大鼠全部存活,缺氧预处理组在造模后24h和48h死亡率为16.3%(9/55)和26%(13/50),明显低于脑出血对照组23.6%(13/55),34%(17/50)。②缺氧预处理组神经行为学评分在造模后6,24h和48h分别为52.64±1.98,52.48±2.99,54.62±2.03,优于脑出血对照组(49.11±2.74,50.76±2.31和52.87±2.75),差异有显著性(P<0.05)。Rosenberg评分缺氧预处理组在6h为3.92±1.59,优于脑出血对照组5.47±1.50(P<0.01)。③脑水含量:缺氧预处理组在造模后24h实验侧基底核脑水含量为(79.96±0.52)%,明显低于脑出血对照组(81.78±1.49)%(P<0.05);缺氧预处理组在造模后48h实验侧基底核脑水含量为(80.49±0.69)%,与脑出血对照组(83.93±1.12)%相比,脑水含量显著降低(P<0.01)。结论:停通气缺氧预处理可以降低脑出血大鼠死亡率,改善神经功能评分,减轻脑水肿。该缺氧预处理方式对脑出血后大鼠具有脑保护作用。

AIM：To observe the effects of asphyxial hypoxic preconditioning on the mortality,neurological symptoms and water content after intracranial hemorrhage in rats, so as to further discuss the cerebral protective effect of hypoxic preconditioning. METHODS：The experiment was performed in Beijing Institute of Neurosurgery from November 2004 to May 2005. Totally 140 male SD rats were randomly allocated into three groups：sham-operated group （n=20）, intracranial hemorrhage control group （n=60） and hypoxic preconditioning group n=60）.Tbe rats were anesthetized with intraperitoneal injection of chloral hydrate, tracheal cannula, vecuronium （2 mg/kg） and mechanical ventilation were given.The rats in the hypoxic preconditioning group were pretreated with four times of preconditioning by stopping ventilation for 1 minute and followed by reventilation far 5 minutes for each circle.One hour later,the tracheal tube was extracted.Models of intracranial hemorrhage were made by stereotactic injection of 50 μl autologous blood into the eaudate nucleus in the hypoxic preconditioning group and intracranial hemorrhage control group,and those in the sham-operated group were injected with saline of the same volume.The circulation was observed within 1 hour after model establishment.The neural deficit scores （NSD） and Rosenberg scores were tested at 6,24,48 and 72 hours after model establishment, and the mortality was calculated. Five survived rats in each group ,acre killed at each time point after anesthesia by cut down head to remove brain, and the brain water content in different brain regions were measured by the wet and dry weight method. RESULTS：Totally 140 rats were successfully made into models, 32 were deleted because of natural death, and finally 108 rats were involved in the analysis of results of NSD and Rosenberg scores tests, 60 rats were used in the detection of brain water content. （1）All the 20 rats in the shamoperated group survived,the mortalities at 24 and 48 hours after model establishment in the hypoxie preconditioning group were obviously lower than those in the intraeranial hemorrhage control group [16.3%（9/55）, 26% （13/50）; 23.6% （13/55）, 34% （17/50）].（2）The NDS scores at 6, 24 and 48 hours after model establishment in the hypoxic preconditioning group were superior to those in the intracranial hemorrhage control group [（52.64±1.98）,（52.48±2.99）,（54.62±2.03）;（49.11±2.74）,（50.76±2.31）, （52.87±2.75）, P〈 0.05].The Rosenberg score at 6 hours in the hypoxic preconditioning group was obviously lower than that in the intracranial hemorrhage control group [（3.92±1.59）,（5.47±1.50）,P 〈 0.01].（3） Brain water content： The brain water content at 24 hours after model establishment in the hypoxie preconditioning group was obviously lower than that in the intracranial hemorrhage control group [（79.96±0.52）%, （81.78±1.49）%,P 〈 0.05]. The brain water content at 48 hours after model establishment in the hypoxic preconditioning group was（80.49±0.69）%,which was significantly decreased as compared with that in the intracranial hemorrhage control group [（83.93±1.12）%,P 〈 0.01]. CONCLUSION：Asphyxial hypoxic preconditioning decreases the mortality, improves NDS and Rosenberg scores, reduces edema degree, and demonstrates cerebral protective effect after intracranial hemorrhage in rats.