發(fā)布時(shí)間：2018-03-04 23:08

  本文選題：神經(jīng)再生　切入點(diǎn)：神經(jīng)生長(zhǎng)因子(NGF)　出處：《南華大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：周圍神經(jīng)損傷在骨科是一種常見的致殘性疾病。周圍神經(jīng)損傷后往往伴有神經(jīng)的缺血缺氧性損傷,特別是擠壓傷后。神經(jīng)再生的過(guò)程實(shí)際上是受損神經(jīng)元形成新的軸突或軸突的生長(zhǎng)延長(zhǎng),再與靶器官重建突觸連接并恢復(fù)其正常功能的過(guò)程。加快周圍神經(jīng)損傷后軸突的再生,對(duì)提高臨床周圍神經(jīng)損傷修復(fù)后療效具有重要意義。免疫抑制藥物他克莫司(FK506)已被發(fā)現(xiàn)在異體手移植的病人上體現(xiàn)出促神經(jīng)生長(zhǎng)的“副”作用,并已表明在實(shí)驗(yàn)?zāi)Ｐ椭芯哂猩窠?jīng)保護(hù)和神經(jīng)營(yíng)養(yǎng)作用,在體內(nèi)外實(shí)驗(yàn)中能增加神經(jīng)突起的延長(zhǎng)和促進(jìn)神經(jīng)再生速率。NGF已經(jīng)被公認(rèn)在神經(jīng)損傷后神經(jīng)再生方面具有神經(jīng)營(yíng)養(yǎng)和神經(jīng)保護(hù)作用。本文通過(guò)構(gòu)建神經(jīng)細(xì)胞缺氧模型,研究了他克莫司(FK506)對(duì)神經(jīng)元突起生長(zhǎng)的影響,探索了FK506協(xié)同神經(jīng)生長(zhǎng)因子(NGF)對(duì)神經(jīng)元突起生長(zhǎng)的促進(jìn)作用,經(jīng)過(guò)一系列的對(duì)比實(shí)驗(yàn),篩選出最佳藥物配比濃度。進(jìn)一步定量檢測(cè)不同濃度FK506在常氧與缺氧狀態(tài)下,分別對(duì)PC12(類神經(jīng)細(xì)胞研究模型)細(xì)胞突起生長(zhǎng)的影響。并通過(guò)蛋白免疫印跡法(Western blotting)檢測(cè)FK506在常氧與缺氧時(shí)對(duì)PC12細(xì)胞HSP70(熱休克蛋白70)、HIF-1ɑ(缺氧誘導(dǎo)因子)表達(dá)的影響,探討FK506保護(hù)缺氧性神經(jīng)元受損的可能性機(jī)制。結(jié)果表明:在缺氧及常氧狀態(tài)下,FK506在1-1000 nmol/L均可協(xié)同NGF促進(jìn)PC12細(xì)胞突起的生長(zhǎng),其中FK506 100 nmol/L與NGF10ng/ml對(duì)缺氧后PC12細(xì)胞突起生長(zhǎng)的協(xié)同作用更明顯。100 nmol/L FK506與10ng/ml NGF對(duì)相關(guān)蛋白表達(dá)具有促進(jìn)作用,100 nmol/L FK506對(duì)PC12細(xì)胞具有缺氧保護(hù)作用,其抗氧化損傷的作用可能與促進(jìn)HSP70、HIF-1ɑ的表達(dá)有關(guān)。該研究對(duì)促進(jìn)周圍神經(jīng)再生速率及對(duì)神經(jīng)受損后缺氧性損傷的治療具有重要的臨床意義。
[Abstract]:Peripheral nerve injury is a common disabling disease in orthopedic department. Especially after crush injury, the process of nerve regeneration is actually the process of injured neurons forming new axons or axons, and then reconstructing synaptic connections with target organs and restoring their normal function, and accelerating the regeneration of axons after peripheral nerve injury. The immunosuppressive drug tacrolimus FK506 has been found to play a "secondary" role in promoting nerve growth in patients with hand allograft. It has been shown that there are neuroprotective and neurotrophic effects in the experimental model. NGF has been recognized to have neurotrophic and neuroprotective effects on nerve regeneration after nerve injury in vivo and in vitro. The effects of tacrolimus FK506) on neuronal process growth were studied. The effects of FK506 and NGF on neuronal neurite growth were investigated, and a series of comparative experiments were conducted to investigate the effect of tacrolimus FK506 on neuronal process growth. The optimal drug concentration was screened out. Further quantitative detection of different concentrations of FK506 in normoxic and anoxic state was carried out. The effects of FK506 on the expression of HSP70 (heat shock protein 70) HIF-1 (hypoxia inducible factor) in PC12 cells during normoxic and hypoxia were detected by Western blotting. To explore the possible mechanism of FK506 protecting hypoxic neurons from injury, the results showed that FK506 could promote the growth of PC12 cell processes in combination with NGF at 1-1000 nmol/L under hypoxia and normoxic conditions. The synergistic effect of FK506 100 nmol/L and NGF10ng/ml on the neurite growth of PC12 cells after hypoxia was more obvious. 100 nmol/L FK506 and 10 ng / ml NGF could promote the expression of related proteins. 100 nmol/L FK506 could protect PC12 cells from hypoxia. This study is of great clinical significance in promoting the regeneration rate of peripheral nerve and the treatment of hypoxic injury after nerve injury.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R688

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