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地塞米松与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].

作者信息

Wang Zhijun, Xu Xing, Wu Xinmin

机构信息

Department of Anesthesiology, Peking University First Hospital, Beijing 100034, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Jun 18;35(3):303-6.

Abstract

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.

摘要

目的

确定地塞米松和甘露醇对大鼠全脑缺血后再灌注损伤的影响。

方法

42只Wistar大鼠随机分为6组:正常组(n = 5),未进行任何手术操作的正常大鼠;假手术组(n = 6),大鼠双侧椎动脉电灼;缺血组(n = 7),双侧椎动脉电灼,双侧颈总动脉用无创动脉夹暂时夹闭10分钟;地塞米松组(n = 8),血管闭塞(VO)后立即腹腔注射地塞米松10 mg·kg-1(体重),每日2次;甘露醇组(n = 8),VO后4小时静脉注射20%甘露醇10 ml·kg-1,每日3次;地塞米松联合甘露醇组(n = 8),腹腔注射地塞米松10 mg·kg-1,每日2次,静脉注射20%甘露醇10 ml·kg-1,每日3次。72小时后处死所有大鼠并取出大脑。从颞叶切取3 mm厚的冠状脑片进行组织病理学检查。用HE染色的石蜡切片测量海马CA1区缺血神经元和神经元密度。用TUNEL法观察细胞凋亡。其余脑组织采用干湿法测量含水量。

结果

所有药物治疗组均能有效减轻脑水肿。地塞米松加重了缺血性神经元损伤,但与其他组相比,地塞米松联合甘露醇是治疗脑缺血损伤最有效的方法。

结论

地塞米松加重脑缺血再灌注损伤,甘露醇对减轻脑缺血再灌注损伤有效,联合用药是最有效的治疗方法。

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