亚低温治疗改善急性颅脑损伤后近期运动功能的机制研究

背景目前已有大量国内外研究显示亚低温能够改善脑缺血和脑创伤后的神经功能预后,然而其脑保护作用的机制尚未明确,尤其尚未深入到分子生物学水平.目的探讨亚低温对脑创伤的治疗作用,并从分子生物学角度探讨其可能的机制.设计随机对照的实验研究.单位北京天坛医院麻醉科、检验科、神经外科.地点和对象实验在首都医科大学附属北京神经外科研究所完成.对42只Wistar大鼠进行研究.42只健康大鼠随机分为3组常温组15只,亚低温组15只和假手术对照组12只.干预常温组和亚低温组用液压装置制成创伤性颅脑损伤(traumaticbrain injury,TBI)侧方打击模型,伤后早期(5 min)脑温分别维持在37～38℃和33～34℃,假手术对照组除不损伤外处理同常温组.控温1h后每组5只立即灌注固定取脑,冷冻切片免疫组织化学方法染色显示c-fos的表达产物Fos蛋白.其余放回动物房,观察24h死亡率并进行运动功能评分.主要观察指标①运动功能评分.②c-fos的表达产物Fos蛋白表达情况.③24h死亡率.结果亚低温组与损伤有关的24 h死亡率(10%)较常温组(60%)明显降低(x2=5.495,P＜0.05),亚低温组前肢肌力、侧方推力、爬坡能力[(3.0±0.7)分,(2.7±0.7)分,(3.0±0.7)分]较常温组[(1.8±1.0)分,(1.5±0.6)分,(1.8±0.5)分]明显改善(t=-2.655,-2.88,3.165,P＜0.05),亚低温组损伤侧皮质Fos的表达(3.0±0.7)较常温组(1.2±0.4)明显增加(t=-4.811,P＜0.01).结论亚低温对TBI有显著的治疗作用,其机制可能与Fos表达增加有关.

Mechanism of subhypothermia therapy for improving the motor function in the near future after acute traumatic brain injury

BACKGROUND: Recently, many reports at home and abroad have indicated that subhypothermia may improve prognosis of nerve function after cerebral ischemia and cerebral injury. But the protection mechanism to brain is not definite. Especially, no research has been done in molecular biological level.OBJECTIVE: To explore subhypothermia therapy to traumatic brain injury and the possible mechanism in molecular biological level.DESIGN: A randomized and controlled study.UNIT: Department of Anesthesiology, Department of Laboratory Medicine,and Department of Neurosurgery in Beijing Tiantan Hospital.SETTING and MATERIALS: The experiment was done in Beijing Neurosurgery Institute affiliated to Capital University of Medical Sciences. Forty-two healthy Wistar rats were randomly divided into 3 groups:Fifteen in normal temperature group, 15 in subhypothermia and 12 in sham-operation group.INTERVENTIONS: The model of traumatic brain injury hit from one side was made by hydraulic equipment in normal temperature group and subhypothermia group. Brain temperature was maintained at 37 ℃ to 38 ℃ and 33 ℃ to 34 ℃ in the early stage(Sminutes) after trauma respectively. The rats in sham-operation group were given the same dealing with normal temperature group except no trauma. After 1 hour temperature control, the brains of five rats in each group were perfused and excised. The expression product of c-Fos, Fos protein was shown by frozen section immunohistochemical staining. The rest rats were put back to the animal house. Death rate in 24hours was observed and motor function score was given.MAIN OUTCOME MEASURe: ① motor function score; ② the expression product of c-Fos, Fos protein expression; ③ Death rate in 24 hours.RESULTS: Death rate in 24 hours related to injury in subhypothermia group (10%) was significantly lower than that in normal temperature group(10% )(x2 = 5. 495, P ＜ 0. 05 ). Muscle force of the front limbs and thrust from one side and climb power in subhypothermia was scored [ (3.0 ± 0.7),(2.7 ± 0. 7), (3.0 ± 0. 7 ) ] which was improved much more than that in normal temperature group[(1.8 ±1.0), (1.5 ±0.6), (1.8 ±0.5)] (t= - 2. 655, - 2. 88, 3. 165, P ＜ 0. 05) . Fos expression of injury side cortex in subhypothermia(3.0 ±0. 7) increased more than that in normal temperature group(1.2 ±0.4)(t = -4.811, P ＜0.01).CONCLUSION: Subhypothermia has therapeutic function to TBI. The mechanism may have some relationship with increase of Fos expression.