摘要
目的观察人白细胞抗原A(HLA A)敲减和酪氨酸羟化酶(TH)过表达的人胚肺成纤维细胞(HELFs)于脑内移植后帕金森病(PD)大鼠的旋转行为和脑内炎性反应。方法用TH反转录病毒和携带HLA A干扰序列的慢病毒(表达绿色荧光蛋白GFP)感染细胞后移植于PD大鼠模型纹状体。移植后检测大鼠旋转行为,免疫组化染色观察TH、OX42、OX6和GFAP表达,GFP观察移植物存活。同时移植HELFs以及TH转导的HELFs和大鼠肺成纤维细胞作对照。结果移植后GFP荧光细胞数量逐渐减少,HLA A敲减组细胞的减少相对较轻,但对大鼠旋转行为的改善不明显;OX42阳性小胶质细胞改变不明显,但OX6表达逐渐增加,而GFAP阳性细胞激活逐渐下降但仍强于移植对侧。结论HLA A表达沉默细胞移植对大鼠运动症状改善不明显,细胞移植能激活小胶质细胞和星形胶质细胞。
Objective Human leukocyte antigen A （HLA A） silencing and tyrosine hydroxylase （TH） over-expressing human embryonic lung fibroblasts （HELFs） were grafted into the striatum of a rat model of Parkinson＇s disease （PD） to observe rotation behavior of the PD rats and inflammation in the brain. Methods The cultured HELFs were transduced with retrovirus carrying TH and lentivirus harboring HLA A siRNA and green fluorescent protein （GFP）, and then grafted into the striatum of PD rats. The rotation behavior was measured, immunostaining for TH, OX42, OX6 and GFAP were performed and GFP was used to evaluate the survival of the grafted cells.HELFs and, HELFs and rat embryonic lung fibroblasts transduced with TH-containing retrovirus were grafted into the brain to serve as controls. Results The GFP fluorenscent cells were gradually reduced after transplantation, and more cells were found in the HLA A silencing HELFs without significant amelioration of rotation behavior. The number of OX42-positive microglia was observed unchangeable, while OX6 cells were gradually increased. Activation of GFAP-positive astrocytes decreased with time, but significantly stronger than that in the contralateral side. Conclusion HLA A silencing does not could induce activation of microglia and promote amelioration of rotation symptom and intracerebral astrocytes transplantation
出处
《基础医学与临床》
CSCD
北大核心
2009年第7期697-703,共7页
Basic and Clinical Medicine
基金
国家自然科学基金(30570567)
北京市自然科学基金(5062004)
