取向纳米纤维神经套管预防创伤性痛性神经瘤形成的机制研究

The management of painful traumatic neuroma has long been a challenge for clinical surgeons with no universally accepted approach. Nerve capping technique is one of the common surgical treatment, but no consistent results have been achieved up to now and its mechanism is still under further investigation. In our previous study, we found that the aligned nanofiber nerve conduit could improve the maturity of SCs, down-regulate the expression levels of TGF-β1 and other cytokines, induce the axial extension of regenerated nerve and collagen fibers and inhibit their over regeneration, contributing to the prevention of traumatic neuroma formation. Based on these findings, our research group puts forward the hypothesis that this nerve capping technique using an aligned nanofiber nerve conduit would generate a certain growth stop signal like a “nerve regeneration brake”, which then suppresses the nerve regeneration and collagen proliferation through RhoA/ROCK and TGF-β1/Smad pathway, respectively. This study is designed to be carried out through detecting the different expression levels of RhoA, ROCK 2 and phosphorylated myosin light chains (p-MLC) in spinal cord and α-SMA ,TGF-β1, Smad 2 and phosphorylated Smad 2 in neuromas using a sciatic nerve model in rats, aiming to explore the possible mechanisms of the nerve capping technique using an aligned nanofiber conduit. The completion of this project may gain insight into the mechanisms of the nerve capping technique in prevention of painful traumatic neuroma formation and may provide a new practical treatment strategy in this field.

创伤性痛性神经瘤的防治始终是困扰临床医生的一大难题，至今仍无切实有效的处置方法。神经套管法是目前常用的一种外科治疗措施，但疗效存在较大差别，尤其是作用机制有待深入研究。本课题组前期研究发现含丝素蛋白的取向纳米神经套管可促进雪旺细胞成熟，下调TGF-β1等细胞因子的表达水平，引导再生神经纤维轴向排列，诱导RhoA基因的高表达、抑制神经过度增生，从而有效抑制神经瘤形成。在此基础上，本课题组提出神经套管法诱导产生“神经再生终止信号”的研究假设，以大鼠坐骨神经为实验模型，通过检测脊髓中RhoA，ROCK 2及磷酸化MLC等基因的表达状况和神经瘤中α-SMA、TGF-β1、磷酸化Smad 2等蛋白的表达水平，深入探讨取向纳米纤维神经套管防止创伤性神经瘤形成及其疼痛产生的具体机制。本课题可为探索神经套管法防治创伤性痛性神经瘤的作用机理提供理论基础，为解决顽固性痛性神经瘤这一临床难题开拓新思路。

创伤性痛性神经瘤的防治始终是困扰临床医生的一大难题，至今仍无切实有效的处置方法 。神经套管法是目前常用的一种外科治疗措施，但疗效存在较大差别，尤其是作用机制有待深 入研究。我们成功建立了动物模型，完成了动物自嗜评分行为学测定及标本大体形态学观察，进一步进行了组织学特性检测以及蛋白组学研究。. 我们发现，α-SMA的表达在神经瘤相关疼痛中起着一定的作用，既可能作为疼痛的直接原因，也可以作为局部机械刺激存在的间接标志。我们还发现，RhoA/ROCK信号通路在创伤性痛性神经瘤的形成过程中起关键作用。在这种情况下，神经套管技术有可能在调节RhoA/ROCK信号通路的基础上产生“再生刹车”。这些发现可能会提供具体的证据，帮助开发治疗痛性神经瘤的新策略。. 上述研究结果为 探索神经套管法防治创伤性痛性神经瘤的作用机理提供理论基础，为解决顽固性痛性神经瘤这 一临床难题开拓新思路。