摘要目的 探讨局部阻断瞬时受体电位阳离子通道亚家族成员V1(TRPV1)表达或功能对大鼠坐骨神经离断伤后轴突再生修复的影响.方法 成年雄性SD大鼠24只,分为4组:正常对照组,单纯损伤组,损伤+AMG-517150μg/kg组及损伤+AMG-517300μg/kg组.在坐骨神经离断损伤的同时,行背根神经节周围注射,用药组注射不同浓度AMG-517,单纯损伤组仅注射等体积溶剂.2周后分别采用酶联免疫吸附测定、Western blot、环氧树脂-半薄切片(1μm)-甲苯胺蓝染色对脊髓后角钙调素基因相关多肽(calcitonin gene-related peptide,CGRP)释放、背根神经节局部TRPV1表达及坐骨神经轴突再生数量和局部微环境变化进行检测.结果 (1)背根神经节周围注射AMG-517可有效阻断脊髓背角CGRP的释放、阻断TRPV1的功能,对照组CGRP为0.15ng/g,单纯损伤组为0.17ng/g,AMG-517150μg/kg组为0.09ng/g,AMG-517300μg/kg组为0.11ng/g(P<0.01);(2)局部阻断TRPV1表达或功能可促进坐骨神经损伤后近端神经轴突的再生(P<0.01);(3)AMG-517可使背根神经节TRPV1的表达下调(P<0.01).结论 (1)周围神经损伤后所引起的TRPV1过度表达或激活可影响周围神经损伤后再生;(2)降低或阻断神经损伤后TRPV1的过度表达或激活有助于周围神经损伤后的修复.

abstractsObjective To observe the effect of the expressive or functional blockage of TRPV1 on nerve regeneration after sciatic trans-section injury. Methods AMG-517, a kind of TRPV1 inhibitor, was injected into the surrounding area of the ipsilateral lumbar dorsal root ganglia while unilateral sciatic nerve was transected. A total of 24 healthy male Sprague-Dawley rats were divided into 4 groups: control group, injury only group,injury+AMG-517 150 μg/kg group,injury+AMG-517 300 μg/kg group. The injury only group was injected the same volume of medium. The release of CGRP from dorsal-horn of spinal cord, the number of axons at proximal stem of sciatic nerve after transection, and the expression of TRPV1 in dorsal root ganglion were detected using the Methods of ELISA, Western blot and semi-thin section(1 μm)-toluidine blue staining 2 weeks after injury. Results The release of CGRP in lumbar spinal dorsal horn was obviously decreased after AMG-517 treatment, which was the evidence of TRPV1 functional inhibition. CGRP in the control group was 0.15 ng/g, the injury only group 0.17 ng/g, AMG-517 150 μg/kg group 0.09 ng/g,and AMG-517 300 μg/kg group 0.11 ng/g(P<0.01). The number of axons which were myelinated or unmyelinated increased after the TRPV1 was inhibited by AMG-517(P<0.01). In addition, the injection of AMG-517 into surrounding dorsal root ganglion decreased the expression of TRPV1 in dorsal root ganglion(P<0.01). Conclusions Over expression or activation of TRPV1 after periphery nerve injury has negative effect on nerve regeneration in fact;Inhibiting the over-expression or over-activation of TRPV1 after nerve injury facilitates axonal regeneration and nerve repair.