【摘要】：目的探討神經(jīng)干細(xì)胞和多巴胺神經(jīng)元聯(lián)合移植改善帕金森病大鼠運(yùn)動(dòng)障礙的效果。方法采用經(jīng)典6-羥基多巴胺毀損法構(gòu)建帕金森病大鼠模型36只,腹腔注射阿樸嗎啡連續(xù)誘導(dǎo)4周。APO注射第4周將36只帕金森病大鼠隨機(jī)分為對(duì)照組、多巴胺組、干細(xì)胞組及聯(lián)合組,每組9只,分別于右側(cè)紋狀體區(qū)立體定向注入生理鹽水、多巴胺神經(jīng)元懸液、神經(jīng)干細(xì)胞懸液、多巴胺神經(jīng)元與神經(jīng)干細(xì)胞懸液。計(jì)算各組移植后2、4、6、8周的旋轉(zhuǎn)次數(shù);干細(xì)胞組及聯(lián)合組分別于移植后1、2、4、8周行MRI掃描,觀察移植區(qū)影像學(xué)變化;移植后8周取各組腦組織行普魯士藍(lán)染色,觀察移植細(xì)胞定植與遷移情況,免疫熒光法檢測(cè)移植細(xì)胞分化情況。結(jié)果移植后2、4、6、8周,對(duì)照組、神經(jīng)干細(xì)胞組、多巴胺組、聯(lián)合組旋轉(zhuǎn)次數(shù)依次降低,組間兩兩比較P均0.01。MRI檢查結(jié)果:隨著時(shí)間延長(zhǎng),聯(lián)合組與干細(xì)胞組移植區(qū)T2 W/FFE成像上呈低信號(hào)影的區(qū)域逐漸變大,但聯(lián)合組低信號(hào)影范圍大于干細(xì)胞組。普魯士藍(lán)染色結(jié)果:干細(xì)胞組和聯(lián)合組移植的神經(jīng)干細(xì)胞及其分化后的細(xì)胞胞質(zhì)內(nèi)均可見(jiàn)大量藍(lán)色顆粒,大部分存留在移植針孔附近,僅少部分細(xì)胞向遠(yuǎn)處遷移,但聯(lián)合組藍(lán)色顆粒數(shù)量以及擴(kuò)散范圍均大于干細(xì)胞組。聯(lián)合組巢蛋白(Nestin)、酪氨酸羥化酶(TH)、綠色熒光蛋白(GFP)陽(yáng)性細(xì)胞數(shù)及Nestin/GFP、TH/GFP均高于干細(xì)胞組,酸性纖維蛋白(GFAP)陽(yáng)性細(xì)胞數(shù)及GFAP/GFP均低于干細(xì)胞組(P均0.01)。結(jié)論神經(jīng)干細(xì)胞與多巴胺神經(jīng)元聯(lián)合移植可顯著改善帕金森病大鼠的運(yùn)動(dòng)障礙,更有助于神經(jīng)干細(xì)胞的定植、遷移及分化成為多巴胺神經(jīng)元。
[Abstract]:Objective to investigate the effect of neural stem cell and dopamine neuron transplantation on motor disorder in Parkinson's disease rats. Methods Thirty-six rats with Parkinson's disease were induced by classical 6-hydroxydopamine damage method. 36 rats were randomly divided into control group and dopamine group by intraperitoneal injection of apomorphine for 4 weeks. Nine rats in each group were injected with normal saline, dopamine neuron suspension, neural stem cell suspension, dopamine neuron and neural stem cell suspension respectively in the right striatum. The rotation times of each group were calculated at 8 weeks after transplantation, MRI scanning was performed in the stem cell group and the combined group at the 1st and 2nd week after transplantation, and the imaging changes in the transplanted area were observed, and Prussian blue staining was performed in the brain tissue of each group at 8 weeks after transplantation. The colonization and migration of transplanted cells were observed, and the differentiation of transplanted cells was detected by immunofluorescence. Results the rotation times of the control group, the neural stem cell group, the dopamine group and the combined group decreased in turn at 8 weeks after transplantation (P < 0.01). The results of MRI showed that the rotation times of the control group, the neural stem cell group, the dopamine group and the combined group decreased in turn. The area of low signal intensity on T 2W / FFE images in the combined group and stem cell group gradually became larger, but the low signal range of the combined group was larger than that of the stem cell group. The results of Prussian blue staining showed that a large number of blue granules were found in the transplanted neural stem cells and their differentiated cytoplasm in stem cell group and combination group, most of them were located near the transplanted pinhole, and only a few of them migrated to the distance. However, the number of blue particles and the diffusion range in the combined group were larger than those in the stem cell group. The number of nestin, tyrosine hydroxylase (th), green fluorescent protein (GFP) positive cells and Nestin / GFP TH- / GFP in combination group were higher than those in stem cell group, and the number of acidic fibrin (GFAP) positive cells and GFAPP / GFP were lower than those in stem cell group (P0.01). Conclusion combined transplantation of neural stem cells and dopamine neurons can significantly improve the motor disorder of Parkinson's disease rats, and it is also helpful to the colonization, migration and differentiation of neural stem cells into dopamine neurons.
【作者單位】： 昆明醫(yī)科大學(xué)第一附屬醫(yī)院;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(81241126,81360197) 云南省教育廳科學(xué)研究基金資助項(xiàng)目(2013C227) 云南省科技廳-昆明醫(yī)學(xué)院聯(lián)合專項(xiàng)(2014FB041)
【分類號(hào)】：R742.5

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