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 ...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.展开更多
基金supported by the National Natural Science Foundation of ChinaNo.81060109+1 种基金a grant from the Yunnan Provincial Department of Science&Technology in ChinaNo.2008CD150
文摘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.
