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高压氧对内皮素-1诱导的大鼠局灶性脑缺血模型的治疗作用

Therapeutic effects of hyperbaric oxygen in a rat model of endothelin-1-induced focal cerebral ischemia.

作者信息

Huang Zhen-Xing, Kang Zhi-Min, Gu Guo-Jun, Peng Guang-Neng, Yun Liu, Tao Heng-Yi, Xu Wei-Gang, Sun Xue-Jun, Zhang John H

机构信息

Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, PR China.

出版信息

Brain Res. 2007 Jun 11;1153:204-13. doi: 10.1016/j.brainres.2007.03.061. Epub 2007 Mar 28.

Abstract

It has been established that hyperbaric oxygen (HBO) treatment reduces brain edema, decreases infarct volume, contributes to neurological functional recovery and suppresses apoptosis in suture-induced focal cerebral ischemic animal models. In the present study, we evaluated the therapeutic effect of HBO in an endothelin-1-induced focal cerebral ischemia in rats and explored the associated mechanisms of HBO-induced brain protection. One hundred twenty male Sprague-Dawley rats (280 to 320 g) were randomly assigned to sham, focal cerebral ischemia and focal cerebral ischemia treated with HBO groups. Brain water content, neurological function, morphology and molecular biological markers were assessed. HBO (100% O2, 2.5 atmosphere absolute for 2 h) was initiated at 1 h after focal cerebral ischemia. Rats were killed at 24 h to harvest tissues for Western blot or for histology. In HBO-treated animals, an enhanced ratio of Bcl-2 and Bax and a reduced expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in the hippocampus after focal cerebral ischemia were observed. These results indicate that HBO provides brain protection that is probably associated with the inhibition of HIF-1alpha and the elevation of Bcl-2.

摘要

业已证实,在缝线诱导的局灶性脑缺血动物模型中,高压氧(HBO)治疗可减轻脑水肿、减小梗死体积、促进神经功能恢复并抑制细胞凋亡。在本研究中,我们评估了HBO对内皮素-1诱导的大鼠局灶性脑缺血的治疗效果,并探讨了HBO诱导脑保护的相关机制。将120只雄性Sprague-Dawley大鼠(280至320克)随机分为假手术组、局灶性脑缺血组和HBO治疗的局灶性脑缺血组。评估脑含水量、神经功能、形态学和分子生物学标志物。局灶性脑缺血后1小时开始进行HBO治疗(100%氧气,绝对压力2.5个大气压,持续2小时)。24小时后处死大鼠,取组织进行蛋白质印迹分析或组织学检查。在接受HBO治疗的动物中,观察到局灶性脑缺血后海马中Bcl-2与Bax的比例增加,缺氧诱导因子-1α(HIF-1α)的表达降低。这些结果表明,HBO提供脑保护作用可能与抑制HIF-1α和提高Bcl-2水平有关。

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