脊髓损伤模型大鼠神经修复与法舒地尔和RhoA基因沉默的干预

背景：研究认为Rho激酶可致使神经生长锥塌陷，对神经修复具有抑制作用。目的：观察Rho激酶抑制剂法舒地尔及RNA干预介导的RhoA基因沉默对脊髓损伤大鼠在体神经损伤修复的作用。方法：雄性SD大鼠60只半切法制成脊髓半横断模型，随机等分成对照组、法舒地尔组和RhoA siRNA组。法舒地尔组于腹腔注射10 mg/kg法舒地尔，2次/d，连续用药1周；RhoA siRNA干扰组将RhoA siRNA表达质粒注射于大鼠脊髓损伤区。结果与结论：伤后4周，法舒地尔和RhoA siRNA组大鼠后肢运动功能均有明显恢复，可见少量神经轴索样结构，辣根过氧化物酶阳性神经纤维数增多(P < 0.05)，体感诱发电位的潜伏期明显缩短、波幅显著增强(P < 0.05)。提示大鼠脊髓损伤后给予Rho激酶抑制剂法舒地尔及RNA介导的RhoA基因沉默能够促进受损伤的脊髓神经功能恢复。

Effect of Fasudil and RhoA gene silencing on nerve repair in a rat model of spinal cord injury

BACKGROUND:Several studies have demonstrated that Rho kinase can lead to collapse of nerve growth cone and exhibits an inhibitory effect on nerve repair. OBJECTIVE:To investigate the effect of Rho kinase inhibitor Fasudil and RNAi-mediated RhoA gene silencing on nerve repair in a rat model of spinal cord injury. METHODS:Sixty male Sprague-Dawley rats were prepared into spinal cord hemisection and then were randomly divided into control, Fasudil and RhoA siRNA groups. The Fasudil group rats were intraperitoneally injected with 10 mg/kg Fasudil, twice a day, for successive 1 week. The RhoA siRNA group rats were injected with RhoA siRNA expression plasmid into spinal cord injury area. RESULTS AND CONCLUSION:At 4 weeks after injection, the hind limb motor function of the Fasudil and RhoA siRNA group rats was obviously recovered, neuronal axon-like structure was observed, horseradish peroxidase-positive nerve fibers were increased (P < 0.05), somatosensory evoked potential latency was obviously shortened, and amplitude was significantly increased (P < 0.05). These results showed that after spinal cord injury, Rho kinase inhibitor Fasudil and RNAi-mediated RhoA gene silencing can promote the neurofunctional recovery of injured spinal cord.