本文關(guān)鍵詞： 激活素A 神經(jīng)生長因子 神經(jīng)突起 5-羥色胺 一氧化氮　出處：《吉林大學(xué)》2008年博士論文　論文類型：學(xué)位論文

【摘要】： 激活素A(Activin A)屬于轉(zhuǎn)化生長因子-β(TGF-β)超家族的多功能生長和分化因子,新的研究揭示,Activin A具有神經(jīng)營養(yǎng)和神經(jīng)保護(hù)作用。但是,Activin A能否促進(jìn)背根神經(jīng)節(jié)(Dorsal root ganglia,DRG)神經(jīng)突起生長、長時(shí)間維持DRG神經(jīng)元存活以及抑制DRG膠質(zhì)細(xì)胞增生作用至今仍不清楚。 本研究采用8日齡雞胚背根神經(jīng)節(jié),體外原代培養(yǎng)法,研究Activin A對(duì)雞胚DRG神經(jīng)突起生長的影響作用。結(jié)果顯示Activin A能夠刺激DRG神經(jīng)突起生長(Neurite outgrowth),通過甲苯胺藍(lán)染色尼氏小體和雙重免疫組織化學(xué)染色證實(shí)Activin A還可以長時(shí)間維持體外培養(yǎng)DRG神經(jīng)元存活以及抑制DRG膠質(zhì)細(xì)胞增生。研究發(fā)現(xiàn)激活素結(jié)合蛋白——卵泡抑素(Follistatin, FS)可以阻斷Activin A促進(jìn)DRG神經(jīng)突起生長和維持DRG神經(jīng)元存活作用,但FS不能阻斷NGF的作用。同時(shí)發(fā)現(xiàn)Activin A與NGF可以協(xié)同促進(jìn)DRG神經(jīng)元神經(jīng)突起生長和維持DRG神經(jīng)元存活。 為了進(jìn)一步探討Activin A作用機(jī)制,實(shí)驗(yàn)采用半定量PCR、液相-質(zhì)譜聯(lián)用儀等,檢測(cè)了激活素II型受體(ActRII)、CGRP、VIP、iNOS mRNA表達(dá)及5-羥色胺和NO釋放情況。結(jié)果顯示,Activin A具有促進(jìn)ActRIIA、CGRP mRNA表達(dá)和神經(jīng)遞質(zhì)5-羥色胺釋放以及抑制NO分泌和iNOS mRNA表達(dá)作用,對(duì)ActRIIB及VIP mRNA表達(dá)無影響。CGRP具有神經(jīng)保護(hù)、5-羥色胺具有促進(jìn)神經(jīng)突起作用,而NO過度分泌可以誘導(dǎo)神經(jīng)細(xì)胞凋亡。上述資料提示Activin A刺激DRG神經(jīng)突起生長和維持神經(jīng)元存活作用,可能與其調(diào)控NO、5-羥色胺釋放及ActRIIA、CGRP表達(dá)有關(guān)。Activin A不僅具有維持神經(jīng)元存活和促進(jìn)神經(jīng)突起生長作用,還可以通過抑制膠質(zhì)細(xì)胞活性改善神經(jīng)組織重構(gòu)、減少瘢痕組織的形成。本研究為Activin A治療神經(jīng)元損傷及變性疾病的應(yīng)用提供了新的數(shù)據(jù)和實(shí)驗(yàn)依據(jù)。
[Abstract]:Activin A is a multifunctional growth and differentiation factor of transforming growth factor- 尾 (TGF- 尾) superfamily. New studies have shown that Activin A has neurotrophic and neuroprotective effects. It is still unclear to maintain the survival of DRG neurons for a long time and to inhibit the proliferation of DRG glial cells. In this study, the dorsal root ganglion (DRG) of 8-day-old chicken embryo was cultured in vitro. The effect of Activin A on the growth of DRG neurite in chicken embryo was studied. The results showed that Activin A could stimulate the growth of DRG neurite. It was proved by toluidine blue staining and double immunohistochemical staining that Activin A could also grow. The survival of DRG neurons was maintained in vitro and the proliferation of DRG glial cells was inhibited. It was found that the activin-binding protein Follistatin (FSA) could block the growth of DRG neurites and maintain the survival of DRG neurons. However, FS could not block the effect of NGF. It was also found that Activin A and NGF could promote the neurite growth of DRG neurons and maintain the survival of DRG neurons. In order to further study the mechanism of Activin A, semi-quantitative Activin and liquid-mass spectrometry were used in the experiment. The expression of iNOS mRNA and the release of 5-hydroxytryptamine and no were detected in ActRII receptor (ActRII). The results showed that Activin A could promote the expression of CGRP mRNA, release of neurotransmitter 5-hydroxytryptamine and inhibit the secretion of no and iNOS mRNA. CGRP has no effect on the expression of ActRIIB and VIP mRNA. CGRP has neuroprotective effects on neuronal processes, while no overexpression can induce neuronal apoptosis. These data suggest that Activin A stimulates the growth of DRG neurites and maintains the survival of neurons. Activin A may be related to the regulation of NO5-HT release and the expression of CGRP in ActRIIAA. Activin A can not only maintain the survival of neurons and promote neurite growth, but also improve the neural tissue remodeling by inhibiting the activity of glial cells. This study provides new data and experimental evidence for the treatment of neuronal injury and degeneration by Activin A.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2008
【分類號(hào)】：R392

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 方琳;柳忠輝;劉永茂;臺(tái)桂香;;激活素促進(jìn)雞胚神經(jīng)節(jié)神經(jīng)突起生長作用[J];動(dòng)物學(xué)雜志;2006年06期

2 湯長華 ,曹曉建 ,王道新;Effects of nerve growth factor on neuronal nitric oxide production after spinal cord injury in rats[J];Chinese Journal of Traumatology;2002年03期

3 方琳;劉永茂;葛敬巖;劉海巖;臺(tái)桂香;柳忠輝;;激活素結(jié)合蛋白阻斷激活素誘導(dǎo)雞胚神經(jīng)節(jié)神經(jīng)突起生長作用及其機(jī)制研究[J];中風(fēng)與神經(jīng)疾病雜志;2007年04期

4 吳俊芳,張均田;Effects of nerve growth factor on nitric oxide-mediated neurotoxicity in primary cortical cultures[J];Chinese Medical Journal;1999年05期

，

本文編號(hào)：1506290