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运动通过诱导大鼠血管生成素-1 和 Tie-2 的表达来改善缺血性脑损伤后的恢复。

Exercise improves recovery after ischemic brain injury by inducing the expression of angiopoietin-1 and Tie-2 in rats.

机构信息

Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, P.R. China.

出版信息

Tohoku J Exp Med. 2011 Jul;224(3):221-8. doi: 10.1620/tjem.224.221.

DOI:10.1620/tjem.224.221
PMID:21701128
Abstract

Post-ischemia angiogenesis plays a critical part in the recovery of neural networks. Angiopoietin (Ang) has received much attention recently due to its key role in neurovascular remodeling. Exercise is proved to contribute to angiogenesis in normal or injured human skeletal muscle. The therapeutic effect of exercise on central angiogenesis after cerebral ischemia, however, has not been studied. In the present study, we investigated the relationship between exercise and the expression of Ang-1, Ang-2, and Tie-2 receptor tyrosine kinase in the brain using a rat model of stroke, with right middle cerebral artery occluded (MCAO). Male Sprague-Dawley rats were randomly grouped (n = 12): stroke-exercise (SE), stroke-no exercise (SNE) and sham-no exercise (SHAM). The SE group ran on a treadmill at a speed of 12 m/min, 30 min/day for 2 weeks. Functional recovery was assessed with neurological evaluation scores. Brain infarction was measured by Nissl staining. Expression of Ang-1, Ang-2, and Tie-2 were compared by immunohistochemical and real-time PCR analyses. The infarct volume in the SE group was significantly reduced compared with the SNE group (p < 0.05). Ang-1 (p < 0.05) and Tie-2 (p < 0.05) and their mRNA expression (p < 0.01 and p < 0.05, respectively) were increased in SE animals at 2 weeks, whereas Ang-2 expression remained unchanged. In conclusion, enhanced expression of Ang-1 and Tie-2 by exercise improves recovery of brain function in MCAO rats. Our results suggest the importance of angiogenesis in rehabilitation for post-ischemia brain injury and help to explain the underlying mechanism.

摘要

缺血后血管生成在神经网络恢复中起着关键作用。血管生成素(Ang)因其在神经血管重塑中的关键作用而受到广泛关注。运动被证明可以促进正常或受损的人类骨骼肌中的血管生成。然而,运动对脑缺血后中枢血管生成的治疗效果尚未研究。在本研究中,我们使用大脑中动脉闭塞(MCAO)的大鼠模型研究了运动与 Ang-1、Ang-2 和 Tie-2 受体酪氨酸激酶在大脑中的表达之间的关系。雄性 Sprague-Dawley 大鼠随机分组(n = 12):中风-运动(SE)、中风-不运动(SNE)和假手术-不运动(SHAM)。SE 组在跑步机上以 12 m/min 的速度运动,每天 30 分钟,持续 2 周。通过神经功能评估评分评估功能恢复。通过尼氏染色测量脑梗死。通过免疫组织化学和实时 PCR 分析比较 Ang-1、Ang-2 和 Tie-2 的表达。与 SNE 组相比,SE 组的梗死体积明显减小(p < 0.05)。在 SE 动物中,Ang-1(p < 0.05)和 Tie-2(p < 0.05)及其 mRNA 表达(分别为 p < 0.01 和 p < 0.05)在 2 周时增加,而 Ang-2 表达保持不变。总之,运动增强 Ang-1 和 Tie-2 的表达可改善 MCAO 大鼠的脑功能恢复。我们的结果表明血管生成在缺血后脑损伤康复中的重要性,并有助于解释潜在的机制。

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