摘要
目的观察大鼠急性脊髓损伤(spinal cord injury,SCI)后芬戈莫德(fingolimod,FTY720)对RhoA表达的影响,进一步探讨FTY720治疗SCI的可能机制。方法采用改良Allen’s法建立大鼠急性SCI模型。雌性SD大鼠75只,随机分为假手术组(n=15)、损伤组(n=30)和FTY720组(n=30)。FTY720组伤后30min一次性腹腔注射FTY7200.5mg/kg,假手术组和损伤组以相同方法给予浓度为0.9%的生理盐水。分别于伤后1天、3天、7天、14天及21天,应用RT-PCR和Western印迹法分别检测RhoA mRNA和RhoA蛋白的表达。结果损伤组RhoA mRNA和蛋白的表达于伤后3天开始明显增加,7天达到高峰,21天仍维持高水平表达;在同一时间点,与FTY720组和假手术组比较,差异有统计学意义(P<0.05)。FTY720组伤后1天、3天和7天的RhoA表达高于假手术组(P<0.05)。假手术组各时间点RhoA表达维持在较恒定水平。结论大鼠急性SCI后RhoA表达增加,FTY720可能通过抑制SCI后RhoA的表达,以达到减轻继发性SCI、促进脊髓神经功能恢复的目的。
Objective To investigate the effect of fingolimod （FTY720） on RhoA expression after spinal cord injury （SCI） in rats, and explore the possible mechanism of FTY720 in the treament of SCI. Methods A rat model of acute SCI was established with a modified Allen＇s method. Seventy-five female Sprague-Dawley （SD） rats were divided randomly into three groups： the sham-operation group （n = 15）, the injury group （n = 30） and the group treated with FTY720 （n = 30）. The FTY720 group received intraperitoneal injections of FTY720 0.5 mg/kg at 30 minutes after SCI, and the sham-operation group and the injury group received 0.9% normal saline in the same way. The expression of RhoA mRNA and protein were detected respectively by RT-PCR and western blotting technique at 1 d, 3 d, 7 d, 14 d and 21 d after SCI. Results The expression of RhoA mRNA and protein in the injury group rose markedly at 3 d, reached a peak at 7 d and still maintained high level at 21 d after injury. The results of the injury group compared to those of the FTY720 and sham-operation groups were statistically different at the same time point （P 0.05）. In addition, the expression of RhoA in the FTY720 group at 1 d, 3 d and 7 d were higher than those in sham-operation group （P 0.05） which kept a constant level throughout the experiment. Conclusion The expression of RhoA increases after acute SCI in rats. FTY720 may attenuate secondary SCI and improve the recovery of neurological function in rats by prohibiting the expression of RhoA after acute SCI.
出处
《中国骨科临床与基础研究杂志》
2010年第4期292-296,共5页
Chinese Orthopaedic Journal of Clinical and Basic Research
