周邊神經再生之神經導管研究:以兔子坐骨神經之25公厘長的神經間隙為動物模式

Peripheral Nerve Regeneration in Nerve Conduits across a 25-mm-long Gap in Rabbits

曾伊聆(I-Ling Tseng)

指導教授 ： 王佩華

共同指導教授 ： 徐善慧

國立臺灣大學/生物資源暨農學院/動物科學技術學研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.03093

摘要

周邊神經損傷是一個嚴重的健康議題，它影響了 2.8 % 的創傷病人。目前對於周邊神經斷傷所產生之神經間隙（gap）的治療方法中，主要包含了自體移植（autograft）及神經導管（nerve conduit）。此研究的目的即藉由適當的評估神經再生方式，了解使用神經導管在兔子的較大神經間隙中修復神經是否有效。試驗以兩種不同處理的導管為試驗組別，自體移植神經為對照組。導管以生物性可降解之聚乳酸聚合物（poly（D,L-lactic acid）, PLA）為材料，製成具不對稱性微孔洞及微溝槽的神經導管。一組導管為未添加任何生物性因子的空導管，另一組導管為添加具有增進神經生長效用的纖維細胞生長因子（fibroblast growth factor 1, FGF1）於導管內面。以24隻公的紐西蘭成兔為試驗動物，隨機分配成三組（自體移植組、神經導管組及添加FGF1的神經導管組），分別在兩個時間點（手術後四及六個月）犧牲。自體移植組在手術時截斷25公厘的坐骨神經，將神經反轉後縫回；兩組神經導管處理組則在手術時則截斷25公厘的神經，並把27公厘的神經導管縫在神經間隙中。手術後每個月進行步態分析試驗。試驗結果顯示，在手術後六個月，上述各處理的恢復率都可達到60 % 以上。另在電生理及組織切片試驗結果顯示，在手術後四及六個月進行運動功能的測試中，顯示自體移植組有較佳的恢復率，但在手術後六個月神經傳導速度中則以有添加FGF1的導管組有較快傳導速度的趨勢。而在腓腸肌的濕重量恢復比率（受傷下肢/未手術下肢）結果顯示在手術後六個月，自體移植組、神經導管組及添加FGF1的神經導管組比率分別是0.82、0.45及0.40，此顯示自體移植組的恢復率顯著比兩組導管組佳。組織切片結果顯示腓腸肌在受傷的腳會有萎縮之現象，但在手術後六個月，此三組的肌纖維面積都顯著比四個月時大，顯示三組的神經的確有在恢復中，使肌肉萎縮情況漸緩。坐骨神經的切片分析，手術後六個月之神經比手術後四個月之神經纖維面積顯著較大（P < 0.05）。綜上所述，神經導管及自體移植組皆能使兔子神經間隙為25公厘的神經再生，且此導管可在三個月內使神經接上。試驗結果顯示對於未來兔子或其他大動物欲發展更穩定的評估神經再生方式，此論文將具有重要參考價值。
關鍵字: 周邊神經損傷、神經導管、自體移植、神經再生

關鍵字

周邊神經損傷 ； 神經導管 ； 自體移植 ； 神經再生

並列摘要

Peripheral nerve injury is a serious health concern for society, affecting 2.8% of trauma patients. Current techniques in peripheral nerve repair include the use of autografts, a golden standard method, and nerve conduits to bridge the nerve gap. The purpose of this study is to evaluate the nerve regeneration across a large gap through nerve conduits in rabbits. In this study, two different conduits were prepared from the same polymer, poly(D,L-lactic acid) (PLA). They were both microporous with novel asymmetric permeability and guiding grooves on the lumen surface. In one type of conduits, acidic fibroblast growth factor 1 (aFGF1) was immobilized on the lumen surface. Twenty-four male adult New Zealand rabbits were used in this study. They were divided into three groups: autograft (control group), NC conduit, and FGF1 conduit. Gait analysis was performed on all animals monthly before the animals were sacrificed. The results indicated that functional recovery percent based on gait analysis was more than 60 % in three groups. The nerve regeneration was evaluated at 4 and 6 months by electrophysiological and histological analysis. Electromyography examination showed better improvement in autograft group. The FGF1 nerve conduit had the fastest nerve conduction velocity 6 months after surgery. The gastrocnemius muscle wet weight ratio (operated site vs. unoperated side) was about 0.82, 0.45, and 0.40 in autograft, NC conduit, and FGF1 conduit groups 6 months after surgery. The ratio of autograft group was significantly higher than two nerve conduit groups. Histomorphology data demonstrated atrophy of the gastrocnemius muscle in the lesion leg while the regenerated fibers of sciatic nerve was distributed as clusters composed of dense myelinated axons. In conclusion, the nerve conduit results were compared to the autograft. The research proved that the PLA nerve conduit could make nerve regenerate through 25-mm-long gap 3 months after surgery.
Keywords: peripheral nerve injury, nerve conduit, autograft, nerve regeneration

並列關鍵字

peripheral nerve injury ； nerve conduit ； autograft ； nerve regeneration

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