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活化的巨噬細(xì)胞在外傷性視神經(jīng)損傷修復(fù)中的作用

發(fā)布時(shí)間:2018-04-30 14:12

  本文選題:視神經(jīng)損傷 + 動(dòng)物模型 ; 參考:《天津醫(yī)科大學(xué)》2012年碩士論文


【摘要】:目的:(1)通過(guò)建立中國(guó)白兔外傷性視神經(jīng)損傷動(dòng)物模型,觀察并比較視神經(jīng)損傷后是否聯(lián)合晶狀體損傷時(shí)視網(wǎng)膜、視神經(jīng)單核/巨噬細(xì)胞浸潤(rùn)與視網(wǎng)膜神經(jīng)節(jié)細(xì)胞軸突再生的關(guān)系,探討單核/巨噬細(xì)胞在視神經(jīng)損傷修復(fù)中的作用。(2)應(yīng)用SPIO作為對(duì)比劑進(jìn)行視網(wǎng)膜、視神經(jīng)磁共振成像,對(duì)視神經(jīng)損傷聯(lián)合晶狀體損傷后單核/巨噬細(xì)胞在組織內(nèi)的遷徙、存活情況進(jìn)行動(dòng)態(tài)觀察,為臨床提供一種通過(guò)動(dòng)態(tài)觀察單核/巨噬細(xì)胞的變化規(guī)律監(jiān)測(cè)視神經(jīng)損傷修復(fù)過(guò)程的新方法。 方法:成年中國(guó)白兔共64只,體重2~2.5kg,選取右眼作為實(shí)驗(yàn)組,左眼作為對(duì)照組,每組各64眼。實(shí)驗(yàn)組(視神經(jīng)聯(lián)合晶狀體損傷組):應(yīng)用液壓沖擊顱腦損傷儀(Fluid Percussion Brain Injury Device, FPI)建立外傷性視神經(jīng)損傷動(dòng)物模型,同時(shí)用半寸針灸針從眼球赤道部垂直刺入鞏膜5~6mm,損傷晶狀體赤道部,建立視神經(jīng)聯(lián)合晶狀體損傷模型。對(duì)照組(單純視神經(jīng)損傷組):應(yīng)用FPI建立單純外傷性視神經(jīng)損傷動(dòng)物模型。每組按照損傷后1、2、4、7、10、14、21、28天等觀察時(shí)間點(diǎn)隨機(jī)分為8個(gè)亞組,每亞組8只。分別在各觀察時(shí)間點(diǎn)之前24h,經(jīng)兔耳緣靜脈注射SPIO (Resovist; Schering, Berlin, Germany),0.2mmol/kg。分別于損傷前及損傷后各觀察時(shí)間點(diǎn)行雙眼閃光視覺(jué)誘發(fā)電位(Flash-Visual Evoked Potential, F-VEP)及視神經(jīng)磁共振成像(Magnetic Resonance Imaging, MRI)檢測(cè);檢測(cè)后摘取雙眼眼球行視網(wǎng)膜、視神經(jīng)組織病理學(xué)特殊染色及免疫組化檢測(cè)。 結(jié)果:(1)F-VEP:實(shí)驗(yàn)組損傷后10天內(nèi)潛伏期逐漸延長(zhǎng)(P0.05),10天后潛伏期逐漸縮短(P0.05);振幅在損傷后7天內(nèi)逐漸降低(P0.05),7天后逐漸升高(P0.05)。對(duì)照組損傷后14天內(nèi)潛伏期逐漸延長(zhǎng)(P0.05),14天后有縮短趨勢(shì)(P0.05);振幅在傷后10天內(nèi)逐漸降低(P0.05),10天后有反彈的趨勢(shì),但是這種反彈趨勢(shì)無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。傷后28天實(shí)驗(yàn)組與對(duì)照組的振幅差異有統(tǒng)計(jì)學(xué)意義(P0.05)。(2)視神經(jīng)MRI:損傷前中國(guó)白兔視神經(jīng)清晰可見(jiàn)呈中等信號(hào),眶內(nèi)結(jié)構(gòu)規(guī)整。損傷后1天右眼晶狀體形狀不規(guī)整,雙眼視神經(jīng)距眼球2.0~4.5mm處信號(hào)增高,眶內(nèi)結(jié)構(gòu)紊亂;損傷后10天中國(guó)白兔右眼視神經(jīng)周?chē)梢?jiàn)大量低信號(hào),而左眼仍以高信號(hào)為主,雙眼視神經(jīng)周?chē)Y(jié)構(gòu)紊亂;損傷后28天中國(guó)白兔雙眼眼視神經(jīng)周?chē)盘?hào)不均,左眼視神經(jīng)周?chē)钥梢?jiàn)少量高信號(hào)。(3)視網(wǎng)膜病理:實(shí)驗(yàn)組損傷后4天視網(wǎng)膜、視神經(jīng)開(kāi)始出現(xiàn)活化的單核/巨噬細(xì)胞,之后逐漸增多,到10天達(dá)到最高峰,10天以后活化的單核/巨噬細(xì)胞數(shù)量逐漸減少,28天后消失;而對(duì)照組各亞組損傷后不同時(shí)間點(diǎn)均未監(jiān)測(cè)到活化的單核/巨噬細(xì)胞。實(shí)驗(yàn)組損傷后4天視網(wǎng)膜開(kāi)始出現(xiàn)軸突再生的視網(wǎng)膜神經(jīng)節(jié)細(xì)胞,之后逐漸增多,而對(duì)照組各亞組損傷后不同時(shí)間點(diǎn)均未監(jiān)測(cè)到軸突再生的視網(wǎng)膜神經(jīng)節(jié)細(xì)胞。 結(jié)論:(1)視神經(jīng)損傷后,活化的單核/巨噬細(xì)胞能夠促進(jìn)RGCs存活和軸突再生,在視神經(jīng)損傷修復(fù)中起著重要作用;(2)應(yīng)用SPIO作為對(duì)比劑進(jìn)行視網(wǎng)膜、視神經(jīng)磁共振成像能夠很好地對(duì)單核/巨噬細(xì)胞在組織內(nèi)的遷徙、存活情況進(jìn)行動(dòng)態(tài)觀察,可用于檢測(cè)視神經(jīng)損傷修復(fù)。
[Abstract]:Objective : ( 1 ) To observe and compare the relationship between retinal and optic nerve mononuclear / macrophage infiltration and retinal ganglion cell axon regeneration after optic nerve injury by establishing the animal model of traumatic optic nerve injury in Chinese white rabbits .

Methods : Sixty adult Chinese rabbits were randomly divided into 8 subgroups according to 1 , 2 , 4 , 7 , 10 , 14 , 21 , 28 days after injury .
After detection , the retina and optic nerve tissue pathology were examined by special staining and immunohistochemistry .

Results : ( 1 ) F - VEP : The latency of F - VEP was gradually prolonged within 10 days after injury ( P0.05 ) .
The amplitude of the control group gradually decreased within 7 days after injury ( P0.05 ) , and gradually increased after 7 days ( P0.05 ) .
There was no significant difference in amplitude between the experimental group and the control group ( P0.05 ) .
There were a lot of low signals around the optic nerve of the right eye of Chinese white rabbits 10 days after injury , while the left eye was still dominated by high signal , and the optic nerve of both eyes was disordered around the optic nerve ;
There was a small number of high signals around the optic nerves around the optic nerve of the eyes of Chinese white rabbits 28 days after injury . ( 3 ) retina pathology : the retina and optic nerve began to appear activated monocytes / macrophages in 4 days after injury , then gradually increased , reached the highest peak in 10 days , the number of activated monocytes / macrophages decreased gradually after 10 days , and disappeared after 28 days ;
In the control group , the activated monocytes / macrophages were not detected at different time points after injury . The retinal ganglion cells with axonal regeneration began to appear in the retina at 4 days after the injury , and the retinal ganglion cells were not detected at different time points after injury in the control group .

Conclusion : ( 1 ) After optic nerve injury , activated monocytes / macrophages can promote the survival and axonal regeneration of RGCs and play an important role in the repair of optic nerve injury ;
( 2 ) Using SPIO as the contrast agent to carry on the retina , the optic nerve magnetic resonance imaging can well observe the migration and survival of the mononuclear / macrophage in the tissue , and can be used for detecting optic nerve injury repair .

【學(xué)位授予單位】:天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類(lèi)號(hào)】:R779.1

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