本文選題：周圍神經(jīng)修復(fù) + 殼聚糖　； 參考：《清華大學(xué)》2015年博士論文

【摘要】：對(duì)于長(zhǎng)段周圍神經(jīng)缺損,導(dǎo)管橋接修復(fù)的臨床效果仍具很大挑戰(zhàn)性。當(dāng)前研究熱點(diǎn)是,研發(fā)各種具有生物學(xué)活性的神經(jīng)導(dǎo)管,不斷提高神經(jīng)損傷的修復(fù)程度。本課題組經(jīng)過(guò)前期研究,已研制出無(wú)抗原性、可控降解的殼聚糖基神經(jīng)修復(fù)導(dǎo)管。本研究立足臨床轉(zhuǎn)化的實(shí)際需求,選取大型哺乳動(dòng)物(山羊)的腓總神經(jīng)作為研究對(duì)象,以長(zhǎng)節(jié)段神經(jīng)缺損為修復(fù)目標(biāo),探索兩種生物活性增強(qiáng)型導(dǎo)管,即殼聚糖導(dǎo)管種植自體骨髓單個(gè)核細(xì)胞和殼聚糖神經(jīng)導(dǎo)管復(fù)合神經(jīng)營(yíng)養(yǎng)因子(NGF、b FGF)緩釋凝膠載體的應(yīng)用可行性。首次采用3.0 T超導(dǎo)型磁共振掃描儀,應(yīng)用一種優(yōu)選掃描序列3D m FFE WATs,聯(lián)合三維后處理技術(shù),觀察山羊腓總神經(jīng)損傷后再生修復(fù)的高場(chǎng)強(qiáng)磁共振影像學(xué)表現(xiàn),探討其在周圍神經(jīng)損傷再生修復(fù)的活體形態(tài)顯示方面的應(yīng)用潛力。從動(dòng)物的行為學(xué)、高場(chǎng)強(qiáng)磁共振神經(jīng)成像、電生理、組織形態(tài)學(xué),免疫組織化學(xué)等方面,觀察神經(jīng)再生與功能恢復(fù)情況。術(shù)后1年結(jié)果顯示:(1)殼聚糖導(dǎo)管+自體骨髓單個(gè)核細(xì)胞,構(gòu)建組織工程化人工神經(jīng),可以修復(fù)山羊腓總神經(jīng)缺損30 mm,效果與自體神經(jīng)移植相似:動(dòng)物行為學(xué)改善至接近正常狀態(tài);再生神經(jīng)的傳導(dǎo)速度與自體神經(jīng)移植組相比,無(wú)顯著性差異;新生神經(jīng)纖維直徑較正常細(xì),髓鞘較正常為薄,密度增大,但再生軸索貫通橋接物全長(zhǎng)。而生理鹽水對(duì)照組未見(jiàn)神經(jīng)明顯再生修復(fù),與骨髓單個(gè)核細(xì)胞組和自體神經(jīng)移植組相比具有顯著差異(p0.05)。(2)殼聚糖導(dǎo)管+NGF/b FGF/肝素/纖連蛋白/纖維蛋白凝膠,成功修復(fù)26 mm神經(jīng)缺損,動(dòng)物行為學(xué)改善明顯,電生理檢測(cè)顯示神經(jīng)傳導(dǎo)改善,組織學(xué)及MRI觀察到神經(jīng)再生顯著且到達(dá)遠(yuǎn)段。而導(dǎo)管鹽水對(duì)照組未見(jiàn)神經(jīng)有效修復(fù),與營(yíng)養(yǎng)因子凝膠組相比具有顯著差異(p0.05)。(3)高場(chǎng)強(qiáng)MRI能夠清晰顯示周圍神經(jīng)損傷及其修復(fù)過(guò)程,可以動(dòng)態(tài)觀察修復(fù)導(dǎo)管局部形態(tài)變化狀況。本研究結(jié)果初步證實(shí),增強(qiáng)型生物活性殼聚糖導(dǎo)管(復(fù)合骨髓單個(gè)核細(xì)胞或NGF/b FGF凝膠),能夠促進(jìn)較長(zhǎng)距離神經(jīng)的再生,并獲得功能修復(fù)。基于統(tǒng)一標(biāo)準(zhǔn)的高度模擬人類的大動(dòng)物周圍神經(jīng)缺損模型,建立客觀量化功能評(píng)價(jià)體系,比較各種生物活性導(dǎo)管之間優(yōu)劣,是下一步研究課題。
[Abstract]:For long peripheral nerve defect, the clinical effect of bridge repair is still very challenging. The current research focus is to develop a variety of biological active nerve conduits to improve the degree of nerve injury repair. After previous research, a non-antigenic and controllable degradation chitosan nerve repair catheter has been developed. In this study, based on the practical needs of clinical transformation, the common peroneal nerve of large mammal (goat) was selected as the research object, and two bioactive enhanced catheters were explored with the long segment nerve defect as the repair target. The feasibility of using chitosan catheter to implant autologous bone marrow mononuclear cells and chitosan nerve conduit combined with NGFGF-FGF-based sustained-release gel carrier was studied. A 3.0T superconducting magnetic resonance scanner was used for the first time to observe the high-field magnetic resonance imaging findings of regeneration and repair of the common peroneal nerve in goats by using a selective 3D FFE WATs and 3D post-processing technique. To explore its application potential in living form display of peripheral nerve regeneration and repair. Nerve regeneration and functional recovery were observed in animal behavior, high field magnetic resonance neurography, electrophysiology, histomorphology and immunohistochemistry. One year after operation, the results showed that the bone marrow mononuclear cells were autologous from the chitosan catheter to construct the tissue engineered artificial nerve. It can repair 30 mm defect of common peroneal nerve in goats, the effect is similar to that of autogenous nerve transplantation, the animal behavior is improved to close to normal state, the conduction velocity of regenerated nerve is not significantly different from that of autogenous nerve transplantation group. The diameter of neonate nerve fibers was finer than that of normal, the myelin sheath was thinner and the density increased, but the regenerated axonal bridging material was full length. There was no obvious nerve regeneration in the saline control group, and there was significant difference between the bone marrow mononuclear cells group and the autologous nerve transplantation group. The chitosan conduit NGF / bFGF- / heparin / fibronectin / fibrin gel was significantly different from that in the bone marrow mononuclear cells group and the autologous nerve transplantation group. The nerve defect of 26 mm was successfully repaired, the animal behavior was improved obviously, the nerve conduction was improved by electrophysiological examination, and the nerve regeneration was observed by histology and MRI. Compared with the nutrition factor gel group, the high field MRI could clearly show the peripheral nerve injury and its repair process, and could dynamically observe the local morphological changes of the repaired ducts. The results showed that the enhanced bioactive chitosan catheter (combined with bone marrow mononuclear cells or NGF / bFGF gel) could promote the regeneration of long distance nerve and obtain functional repair. The next step is to establish an objective quantitative function evaluation system based on the unified standard model which highly simulates the human peripheral nerve defect in large animals and to compare the merits and demerits of various bioactive catheters.
【學(xué)位授予單位】：清華大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R651.3

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相關(guān)期刊論文 前1條

1 張衛(wèi)國(guó);呂德成;傅重洋;曲巍;;殼聚糖復(fù)合他克莫司緩釋鞘管促進(jìn)大鼠坐骨神經(jīng)再生的實(shí)驗(yàn)研究[J];中華醫(yī)學(xué)雜志;2006年15期

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本文編號(hào)：2018842