中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (11): 1836-1840.doi: 10.4103/1673-5374.170314

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

法舒地尔和塞来昔布联用促进损伤脊髓功能恢复优于单一用药

  

  1. Xiao-lin Hou1, Yan Chen1, Hua Yin1, Wei-gang Duan1, 2, *
  • 收稿日期:2015-06-16 出版日期:2015-12-07 发布日期:2015-12-07
  • 基金资助:

    中国国家自然科学基金项目(81060109),云南省科技基金项目(2008CD150)

Combination of fasudil and celecoxib promotes the recovery of injured spinal

  1. 1 Key Laboratory of Molecular Biology for Sinomedicine, Yunnan Key Laboratory for Enthnomedicine, Kunming, Yunnan Province, China
    2 Initiative Team of Microenvironment, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China
  • Received:2015-06-16 Online:2015-12-07 Published:2015-12-07
  • Contact: Wei-gang Duan, Ph.D.,deardwg@126.com.
  • Supported by:

    The study was supported by the National Natural Science Foundation of China, No. 81060109, and a grant from the Yunnan Provincial Department of Science & Technology in China, No. 2008CD150.

摘要:

Rho激酶抑制剂的耐药机制与环氧合酶2增强有关,因而我们推测其治疗神经疾病的作用可被环氧合酶2抑制剂强化。实验为观察Rho激酶抑制剂法舒地尔和环氧合酶2抑制剂塞来昔布对大鼠脊髓损伤的协同效应。以T11右半侧横断损伤建立大鼠脊髓损伤模型,连续2周腹腔注射塞来昔布(20 mg/kg)和/或法舒地尔(10 mg/kg)。结果显示,联合使用塞来昔布和法舒地尔可以明显降低大鼠脊髓损伤部位附近环氧合酶2和Rho激酶 II的表达,改善脊髓损伤的病理形态,促进运动功能恢复,且效果优于塞来昔布或法舒地尔单独治疗。表明Rho激酶抑制剂和环氧合酶2抑制剂的组合应用能协同促进脊髓损伤的运动功能恢复。

关键词: 神经再生, Rho激酶, 法舒地尔, 环氧合酶2, 塞来昔布, 脊髓损伤

Abstract:

Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.

Key words: nerve regeneration, Rho kinase, fasudil, cyclooxygenase-2, celecoxib, spinal cord injury, NSFC grant, neural regeneration