取向纳米神经导管预防创伤性神经瘤的形成及其机理研究

发布时间：2018-04-15 11:40

本文选题：创伤性神经瘤 + 神经套管法　；参考：《上海交通大学》2014年博士论文

【摘要】：目的创伤性痛性神经瘤的防治一直是困扰临床医生的一大难题，神经套管法是目前较为有效的治疗方法，但由于神经套管材料的限制，使该治疗方法至今仍未推广应用。本课题拟研究生物可降解的取向纳米纤维神经导管对创伤性痛性神经瘤的防治作用，并探讨其相关作用机理，为临床上处理这一棘手难题提供理论支持和新的治疗策略。方法首先，利用静电纺丝技术，制备取向及无规纳米纤维支架，观察雪旺氏细胞（SCs）在不同支架上的生长状况及形态差异，检测纤维支架不同地貌特征对SCs成熟度以及细胞因子表达水平的影响；其次，将纳米纤维支架制备成神经导管，以SD大鼠坐骨神经为实验模型，从其自嗜行为、瘤体重量增长比（WIR）、形态学以及组织学的变化等研究纳米神经导管对神经瘤的形成及其疼痛状态的影响；最后，通过比较分析取向纳米导管对神经瘤组织的形态学、分子生物学及动物疼痛状态的影响，研究其预防痛性神经瘤形成的可能作用机理。结果 SCs在取向纳米纤维上沿着纤维轴向生长和拉长，而在无规纤维上则呈多边形、杂乱性的扩散形貌；在取向纳米纤维上培养的SCs的成熟度显著优于在无规纳米纤维上培养的SCs，而且其TGF-β1及NGF等细胞因子的表达水平也相应显著下调（P0.001）；动物实验显示，WIR、自嗜评分及疼痛相关蛋白的表达水平等各项指标以无套管组为最高，无规组次之,取向组最低（P0.01）；进一步研究表明，取向组中再生神经纤维及SCs与无套管组相比更加成熟，NGF等细胞因子的分泌水平也大幅下调，腰4背根神经节中RhoA基因的表达水平也显著高于无套管组,而-平滑肌肌动蛋白(-SMA)的表达水平却显著低于无套管组（P0.001）。结论取向纳米神经导管可引导再生神经纤维的轴向延伸，促进新生纤维的成熟，从而可能诱发了阻止神经瘤增长的再生终止信号，并抑制了-SMA（可自发收缩）及NGF（可作为一种疼痛介质）的表达，从而抑制了神经瘤的形成及疼痛的发生。取向纳米神经导管对解决创伤性痛性神经瘤这一临床难题提供了新的治疗策略，，具有广阔的应用前景。
[Abstract]:PurposeThe prevention and treatment of traumatic painful neuroma has been a difficult problem for the clinicians. The nerve cannula method is an effective treatment method at present, but because of the limitation of the nerve cannula material, the treatment method has not been popularized up to now.The purpose of this study is to study the preventive and therapeutic effects of biodegradable oriented nanofiber nerve conduit on traumatic pain neuroma, and to explore its related mechanism, and to provide theoretical support and new therapeutic strategies for clinical treatment of this thorny problem.MethodFirstly, the orientation and random nanofiber scaffolds were prepared by electrospinning technique to observe the growth status and morphological differences of Schwann cells on different scaffolds.The effects of different geomorphological features on SCs maturity and cytokine expression were examined. Secondly, the nerve conduit was prepared from the nanofiber scaffold and the sciatic nerve of SD rats was used as the experimental model.The effects of nanotubes on the formation and pain state of neuroma were studied by means of morphological and histological changes.The effects of molecular biology and animal pain state on the possible mechanism of preventing the formation of painful neuroma were studied.ResultSCs grows and elongates along the fiber axis on the oriented nanofibers, while on the random fibers, it is polygonal, disorderly and diffusive.The maturity of SCs cultured on oriented nanofibers was significantly better than that of SCS cultured on random nanofibers, and the expression level of cytokines such as TGF- 尾 1 and NGF was significantly down-regulated P0.001.The animal experiments showed that SCs, self-eosinophilic score and pain were significantly decreased.The expression level of related proteins was the highest in the tube-free group.Further studies showed that the levels of regenerated nerve fibers and SCs in the orientation group were significantly lower than those in the non-trocar group, and the levels of cytokines such as NGF in the orientation group were significantly lower than those in the trocar free group.The expression level of RhoA gene in lumbar 4 dorsal root ganglion was significantly higher than that in trocar free group, while the expression level of -smooth muscle actin (SMA) was significantly lower in lumbar 4 dorsal root ganglion than that in trocar free group (P 0.001).ConclusionOriented nanotubes can guide the axial extension of regenerated nerve fibers and promote the maturation of new fibers, which may induce a signal of termination of regeneration that prevents the growth of neuroma.It also inhibited the expression of SMA (spontaneous contraction) and NGF (as a kind of pain medium), which inhibited the formation of neuroma and the occurrence of pain.The oriented nanotube provides a new strategy for the treatment of traumatic painful neuroma, and has a broad application prospect.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R651;R318.08

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