人羊膜上皮细胞移植入半侧帕金森病大鼠侧脑室的治疗效果。
Therapeutic effect of human amniotic epithelial cell transplantation into the lateral ventricle of hemiparkinsonian rats.
机构信息
Department of Neurology, First Affiliated Hospital of SooChow University, Suzhou, Jiangsu 215006, China.
出版信息
Chin Med J (Engl). 2009 Oct 20;122(20):2449-54.
BACKGROUND
Human amniotic epithelial cells (HAECs) are able to secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine neurons. Previous study showed that when human amniotic epithelial cells were transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-induced Parkinson disease rats, the cells could survive and exert functional effects. The purpose of this study was to investigate the survival and the differentiation of human amniotic epithelial cells after being transplanted into the lateral ventricle of Parkinson's disease (PD) rats, and to investigate the effects of grafts on healing PD in models.
METHODS
The Parkinson's model was made with stereotactic microinjection of 6-hydroxydopamine (6-OHDA) into the striatum of a rat. The PD models were divided into two groups: the HAECs group and the normal saline (NS) group. Some untreated rats were taken as the control. The rotational asymmetry induced by apomorphine of the HAECs group and the NS group were measured post cell transplantation. The expression of nestin and vimentin in grafts were determined by immunohistology. Ten weeks after transplantation the density of tyrosine hydroxylase positive cells in the substantia nigra of the HAECs group, NS group and the untreated group was determined. The differentiation of grafts was determined by TH immunohistology. High performance liquid chromatography (HPLC) was used to determine monoamine neurotransmitter levels in the striatum.
RESULTS
The rotational asymmetry induced by apomorphine of the HAECs group was ameliorated significantly compared to the NS group two weeks after transplantation (P < 0.01). The grafts expressed nestin and vimentin five weeks after transplantation. TH immunohistochemistry indicated that the TH positive cells in the substantia nigra of the HAECs group increased significantly compared to the NS group (P < 0.01). Tyrosine hydroxylase (TH) positive cells in the substantia nigra of the HAEC group and the NS group were decreased compared to the untreated group (P < 0.01). Dopamine and DOPAC levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.05). Homovanillic acid (HVA) levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.01). In addition dopamine, DOPAC, and HVA levels in the striatum and dopamine levels in the cerebrospinal fluid of the HAECs group and the NS group were decreased compared to the untreated group (P < 0.05).
CONCLUSIONS
Human amniotic epithelial cells could be used to ameliorate the rotational asymmetry induced by apomorphine of the PD models. This could have been due to the increased content of dopamine and its metabolic products, DOPAC and HVA, in the striatum in the PD models.
背景
人羊膜上皮细胞（HAECs）能够分泌具有生物活性的神经营养因子，如脑源性神经营养因子和神经营养因子-3，两者均对多巴胺神经元表现出营养作用。先前的研究表明，当人羊膜上皮细胞被移植到 6-羟多巴胺（6-OHDA）诱导的帕金森病大鼠纹状体中时，细胞可以存活并发挥功能作用。本研究的目的是研究人羊膜上皮细胞在帕金森病（PD）大鼠侧脑室移植后的存活和分化情况，并探讨移植物对模型中 PD 愈合的影响。
方法
用立体定向微注射 6-羟多巴胺（6-OHDA）制作帕金森模型。PD 模型分为 HAECs 组和生理盐水（NS）组两组。一些未经处理的大鼠作为对照。细胞移植后，通过阿朴吗啡诱导的旋转不对称性测量 HAECs 组和 NS 组的旋转不对称性。通过免疫组织化学检测移植物中巢蛋白和波形蛋白的表达。移植后 10 周，测定 HAECs 组、NS 组和未处理组黑质内酪氨酸羟化酶阳性细胞的密度。通过 TH 免疫组织化学法测定移植物的分化情况。高效液相色谱法（HPLC）测定纹状体中单胺神经递质水平。
结果
移植后两周，HAECs 组阿朴吗啡诱导的旋转不对称性明显改善，与 NS 组相比差异有统计学意义（P<0.01）。移植后 5 周，移植物表达巢蛋白和波形蛋白。TH 免疫组化显示，HAECs 组黑质内 TH 阳性细胞明显多于 NS 组（P<0.01）。HAECs 组和 NS 组黑质内酪氨酸羟化酶（TH）阳性细胞较未处理组减少（P<0.01）。HAECs 组纹状体中多巴胺和 DOPAC 水平明显高于 NS 组（P<0.05）。HAECs 组纹状体中高香草酸（HVA）水平明显高于 NS 组（P<0.01）。此外，HAECs 组和 NS 组纹状体中多巴胺、DOPAC 和 HVA 水平以及脑脊液中多巴胺水平均低于未处理组（P<0.05）。
结论
人羊膜上皮细胞可用于改善 PD 模型中阿朴吗啡诱导的旋转不对称性。这可能是由于纹状体中多巴胺及其代谢产物 DOPAC 和 HVA 的含量增加。
Zotero 插件