Clenbuterol，β_2-肾上腺素能受体激动剂促进成年大鼠脊髓半横切后红核脊髓束轴突再生和运动功能的恢复

目的研究Clenbuterol对于促进脊髓半横切(SCI)后轴突再生和运动功能恢复的功效。方法成年Wistar大鼠(n=10-12)接受硬脊膜内的第7颈段脊髓单侧半横切显微手术。Clenbuterol以9 mg/L的剂量加入饮用水中,而对照组未给予任何治疗。采用Cylinder试验和患肢抓力试验观察运动功能的恢复状况。行为学观察期(6周)结束后,大鼠接受第二胸段脊髓处椎板切开术,4%Fluorogold微量注射进入红核脊髓束,一周后被处死。结果运动功能逐渐恢复,从SCI后第3周开始,Clenbuterol治疗组显著优于对照组(最终患肢抓力:403.45±19.82g vs 335.13±13.48g,p<0.05);在Cylinder试验中,双侧前肢共同使用触壁的百分比,Clenbuterol组显著高于对照组(43.39%±5.85%vs 19.42%±6.61%,p<0.05)。Clenbuterol治疗显著地降低了SCI后继发性组织损伤,提高了pCREB阳性细胞核在整个SCI点的表达水平。与对照组相比,Clenbuterol显著地促进了红核脊髓束轴突的再生。结论脊髓损伤后,Clenbuterol可促进离断的轴突再生以及运动功能的恢复。

Clenbuterol,β2-Adrenoreceptor Agonist Improves Regeneration of Rubrospinal Axons and Recovery of Locomotor Function after Spinal Cord Hemisection in Adult Rats

Objective To explore the efficacy of Clenbuterol(β_2-adrenoreceptor agonist)to promote axonal regeneration and recovery of locomotor function after spinal cord injury(SCI).Methods Wistar rats(n=10-12)received a unilateral hemisection within the dura mater at C7 spinal cord segment.Clenbuterol was administered by adding it to the drinking water at a dose of 9 mg/L.Locomotor function was observed with Cylinder test and Grip strength test.For retrograde axonal tracing,after the predetermined period of observation(6 weeks),rats underwent laminectomy at T2 and 4% Fluorogold was injected into rubrospinal tract(RST).The rats were sacrificed 1 week later.Results Locomotor function progressive recovery started to become apparent at 3 weeks after injury and was significantly greater in Clenbuterol treatment group compared to the untreated controls(final Grip force:403.45±19.82g vs 335.13±13.48g,p<0.05),and Clenbuterol treated animals used both forelimbs more frequently for vertical exploration(43.39%±5.85% vs 19.42%±6.61%,p<0.05). Clenbuterol treatment significantly decreased secondary damage after SCI and increased the pCREB positive nuclei throughout the hemisection site.Retrograde axonal tracing revealed that Clenbuterol enhanced the regeneration of RST axons.Conclusion Clenbuterol promotes the regeneration of axotomized axons and recovery of locomotor function after SCI.