本文選題：創(chuàng)傷性神經(jīng)瘤 + 神經(jīng)套管法　； 參考：《上海交通大學(xué)》2014年博士論文

【摘要】：目的 創(chuàng)傷性痛性神經(jīng)瘤的防治一直是困擾臨床醫(yī)生的一大難題，神經(jīng)套管法是目前較為有效的治療方法，但由于神經(jīng)套管材料的限制，使該治療方法至今仍未推廣應(yīng)用。本課題擬研究生物可降解的取向納米纖維神經(jīng)導(dǎo)管對創(chuàng)傷性痛性神經(jīng)瘤的防治作用，并探討其相關(guān)作用機理，為臨床上處理這一棘手難題提供理論支持和新的治療策略。 方法 首先，利用靜電紡絲技術(shù)，制備取向及無規(guī)納米纖維支架，觀察雪旺氏細胞（SCs）在不同支架上的生長狀況及形態(tài)差異，檢測纖維支架不同地貌特征對SCs成熟度以及細胞因子表達水平的影響；其次，將納米纖維支架制備成神經(jīng)導(dǎo)管，以SD大鼠坐骨神經(jīng)為實驗?zāi)Ｐ�，從其自嗜行為、瘤體重量增長比（WIR）、形態(tài)學(xué)以及組織學(xué)的變化等研究納米神經(jīng)導(dǎo)管對神經(jīng)瘤的形成及其疼痛狀態(tài)的影響；最后，通過比較分析取向納米導(dǎo)管對神經(jīng)瘤組織的形態(tài)學(xué)、分子生物學(xué)及動物疼痛狀態(tài)的影響，研究其預(yù)防痛性神經(jīng)瘤形成的可能作用機理。 結(jié)果 SCs在取向納米纖維上沿著纖維軸向生長和拉長，而在無規(guī)纖維上則呈多邊形、雜亂性的擴散形貌；在取向納米纖維上培養(yǎng)的SCs的成熟度顯著優(yōu)于在無規(guī)納米纖維上培養(yǎng)的SCs，而且其TGF-β1及NGF等細胞因子的表達水平也相應(yīng)顯著下調(diào)（P0.001）；動物實驗顯示，WIR、自嗜評分及疼痛相關(guān)蛋白的表達水平等各項指標(biāo)以無套管組為最高，無規(guī)組次之,取向組最低（P0.01）；進一步研究表明，取向組中再生神經(jīng)纖維及SCs與無套管組相比更加成熟，NGF等細胞因子的分泌水平也大幅下調(diào)，腰4背根神經(jīng)節(jié)中RhoA基因的表達水平也顯著高于無套管組,而-平滑肌肌動蛋白(-SMA)的表達水平卻顯著低于無套管組（P0.001）。 結(jié)論 取向納米神經(jīng)導(dǎo)管可引導(dǎo)再生神經(jīng)纖維的軸向延伸，促進新生纖維的成熟，從而可能誘發(fā)了阻止神經(jīng)瘤增長的再生終止信號，并抑制了-SMA（可自發(fā)收縮）及NGF（可作為一種疼痛介質(zhì)）的表達，從而抑制了神經(jīng)瘤的形成及疼痛的發(fā)生。取向納米神經(jīng)導(dǎo)管對解決創(chuàng)傷性痛性神經(jīng)瘤這一臨床難題提供了新的治療策略，，具有廣闊的應(yīng)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.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R651;R318.08

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