中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (3): 438-444.doi: 10.4103/1673-5374.153693

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

SMADs对脑缺血再灌注损伤的神经保护

  

  • 收稿日期:2015-02-12 出版日期:2015-03-20 发布日期:2015-03-20

Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion

Fang-fang Liu 1, Chao-ying Liu 2, Xiao-ping Li 3, Sheng-zhe Zheng 4, Qing-quan Li 5, Qun Liu 1, Lei Song 2   

  1. 1 Department of Neurology, First Hospital of Jilin University, Changchun, Jilin Province, China
    2 Department of Respiratory Medicine, First Hospital of Jilin University, Changchun, Jilin Province, China
    3 Department of Pediatrics, First Hospital of Jilin University, Changchun, Jilin Province, China
    4 Department of Neurology, Affiliated Hospital of Yanbian University, Yanbian, Jilin Province, China
    5 Department of Hepatic-Biliary-Pancreatic Medicine, First Hospital of Jilin University, Changchun, Jilin Province, China
  • Received:2015-02-12 Online:2015-03-20 Published:2015-03-20
  • Contact: Lei Song, M.D., Ph.D., or Qun Liu, M.D., Ph.D., l.song@139.com or songlei@163.com
  • Supported by:

     This work was supported by the National Natural Science Foundation of China, No. 81460193.

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摘要：

既往研究已证实，转化生长因子β1的上调对脑缺血有神经保护作用，但其下游分子SMAD2/3对脑缺血再灌注损伤的作用尚不明确。实验旨在分析脑缺血再灌注大鼠大脑SMAD2/3表达与细胞凋亡和炎症反应的关系，并欲证明其具有神经保护作用。结果显示，大鼠脑缺血再灌注损伤后6h缺血半暗带中SMAD2/3 mRNA表达明显上调，72h达到高峰。磷酸化SMAD2/3蛋白表达随时间的变化与mRNA一致。腺病毒介导的SMAD3过表达降低了缺血大脑组织炎症因子肿瘤坏死因子α 和白细胞介素1β mRNA表达，下调了凋亡执行者capase-3表达，上调了抗凋亡蛋白Bcl-2的表达。SMAD3蛋白表达与细胞凋亡呈负相关。说明SMAD3通过抗炎和抗凋亡途径，对缺血再灌注脑组织起到了神经保护效应。

关键词: 神经再生, 脑损伤, 神经保护, 炎症, 凋亡, 脑缺血, SMAD, 转化生长因子β1

Abstract:

Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.

Key words: nerve regeneration, brain injury, neuroprotection, inflammation, apoptosis, cerebral ischemia, SMAD3, transforming growth factor β1v NSFC grant, neural regeneration