地塞米松、甘露醇对大鼠全脑缺血再灌注损伤的治疗作用

Therapeutic effect of dexamethasone and mannitol on global brain ischemia-reperfusion injury in rats

目的 :观察地塞米松、甘露醇对缺血再灌注损伤脑组织的作用。方法 :Wistar大鼠 4 2只 ,随机分为 6组 ,正常对照组 (n =5 ) ;假手术组 (n =6 ) ,仅电凝双侧椎动脉 ;缺血对照组 (n =7) ,电凝双侧椎动脉 ,夹闭双侧颈总动脉 10min后恢复脑血流灌注 ;地塞米松治疗组 (n =8) ,脑缺血复灌后腹腔注射地塞米松 10mg·kg-1,每日 2次 ;甘露醇治疗组 (n =8) ,脑缺血复灌后尾静脉注射 2 0 % (体积分数 )甘露醇 10ml·kg-1,每日 3次 ;地塞米松复合甘露醇治疗组 (n =8)脑缺血复灌后腹腔注射地塞米松 10mg·kg-1,每日 2次 ,同时给予 2 0 %甘露醇 10ml·kg-1,尾静脉注射 ,每日 3次。 6组均于 72h后断头取脑 ,于颞叶最宽处切取 3mm厚冠状面脑组织切片 ,行病理HE染色和TUNEL染色 ,计数海马区神经元密度和缺血细胞。其余脑组织行干—湿称重法测脑水含量。结果 :各药物处理组均能有效减轻脑水肿。与其他处理组比较 ,地塞米松处理组缺血性脑损伤表现最严重 ,而在地塞米松复合甘露醇处理组脑损伤表现最轻。结论 :地塞米松可加重脑缺血再灌注损伤 ,甘露醇具有确切的减轻再灌注脑损伤的作用 。

Objective: To determine the effect of dexamethasone and mannitol on reperfusion injury after global brain ischemia in rats.Methods:Forty two Wistar rats were randomly divided into six groups:normal group ( n =5),normal rats without any surgical operation; sham operative group ( n =6), the rat bilateral vertebral arteries were electrocauterized; ischemia group ( n =7), bilateral vertebral arteries were electrocauterized, and both carotid arteries were occluded temporarily by atraumatic artery clasp for 10 minutes; dexamethasone group ( n =8), intraperitoneal dose of dexamethasone of 10 mg·kg -1 (body weight)was received immediately after vessel occlusion (VO), twice a day; mannitol group ( n =8),intravenous dose of 20% mannitol of 10 ml·kg -1 was received 4 hours after VO,three times a day; dexamethasone combined with mannitol group ( n =8),both intraperitoneal dexamethasone of 10 mg·kg -1 , twice a day, and intravenous 20% mannitol of 10 ml·kg -1 , three times a day were administered. All rats were sacrificed and brains were removed after 72 hours. A 3 mm thick coronal brain was sliced from temporal lobe for histopathological examination. Ischemic neurons and neuron density in hippocampal CA1 region were measured with paraffin sections stained by HE methods. Apoptosis of cells was observed by TUNEL method.The rest of the brain was used to measure water contents by means of wet-dry method. Results: All drug treated groups could effectively reduce brain edema. Dexamethasone exacerbated ischemic neuronal injury but dexamethasone combined with mannitol was the most effective treatment for brain ischemia injury compared with other groups. Conclusion: Dexamethasone aggravates brain ischemic reperfusion injury,mannitol is effective for reducing brain ischemia reperfusion injury,and application of the combined agents is the most effective treatment.