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 (4): 568-575.doi: 10.4103/1673-5374.155429

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

白藜芦醇抑制基质金属蛋白酶减轻脑缺血神经元损害：神经保护作用的分子对接研究

  

  • 收稿日期:2015-02-14 出版日期:2015-04-22 发布日期:2015-04-22

Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia: a molecular docking study exploring possible neuroprotection

Anand Kumar Pandey 1, Pallab Bhattacharya 1, 2, Swet Chand Shukla 3, Sudip Paul 1, 4, Ranjana Patnaik 1   

  1. 1 School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India
    2 Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
    3 School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India
    4 Department of Biomedical Engineering, North Eastern Hill University (NEHU), Shillong, India
  • Received:2015-02-14 Online:2015-04-22 Published:2015-04-22
  • Contact: Anand Kumar Pandey, Ph.D. or Ranjana Patnaik, Ph.D., pandayanandkumar@gmail.com or rpatnaik11@gmail.com.

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摘要：

白藜芦醇是一种可有效阻止与脑缺血相关的细胞进程的药物，基质金属蛋白酶已被证实是药物干预脑缺血的潜在靶点。我们试图通过分子对接研究探讨白藜芦醇与基质金属蛋白酶的相互作用。在建立脑缺血再灌注损伤大鼠模型前30min和建模后2h腹腔注射白藜芦醇，见模型大鼠的神经功能和脑水肿明显改善，脑梗死体积明显缩小，大脑皮质和纹状体亚硝酸盐和丙二醛水平明显下降。白藜芦醇与基质金属蛋白酶的分子对接研究显示，白藜芦醇占据了基质金属蛋白酶2和9的活性位点。基质金属蛋白酶2和9的复合物结合能分别是37.848672 和 -36.6345kJ/mol。说明白藜芦醇可通过抑制基质金属蛋白酶2和9的活性，对脑缺血起到神经保护作用。

关键词: 神经再生, 神经保护, 白藜芦醇, 脑缺血, 脑梗死, 基质金属蛋白酶, 分子对接, 细胞外基质

Abstract:

The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases (MMPs) has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the interaction of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neurological function and brain edema were significantly alleviated, cerebral infarct volume was significantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were significantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was –37.848672 kJ/mol and –36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These findings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

Key words: nerve regeneration, neuroprotection, resveratrol, cerebral ischemia, cerebral infarction, matrix metalloproteinase, molecular docking, extracellular matrix, neural regeneratio