微囊化人视网膜色素上皮细胞移植治疗帕金森病的实验研究

Transplantation of microencapsulated human retinal pigment epithelial cells in Parkinsonian rats

目的观察微囊化人视网膜色素上皮（RPE）细胞移植治疗帕金森病（PD）大鼠的疗效。方法采用机械分离法和酶消化法原代培养人RPE细胞，传代后用高压静电微胶囊成型装置制作海藻酸钠-多聚赖氨酸-海藻酸钠微囊化细胞．将其立体定向移植人6-羟基多巴胺（6-OHDA）所致的PD模型大鼠的右侧纹状体。实验分为模型组、裸细胞（RPE）组、空囊对照（APA）组以及微囊化细胞（APA—RPE）组。检测各组大鼠移植前后阿朴吗啡诱导的旋转行为变化和移植后8周纹状体中多巴胺fDA）的含量。结果APA—RPE组大鼠在移植后4周阿朴吗啡诱发的旋转次数[（6．25±1．04）r／min]开始减少，与移植前[（12．88±7．34）r／min]相比减少幅度为51．48％，至第8周[（5．87±2．03）dmin]减少更加明显，减少幅度为54．43％，差异均有统计学意义（P〈0．05）；与模型组[（108．14±1．89）mol／L]比较，APA—RPE组移植后8周[（342．63±28．32）mol／L]大鼠纹状体DA含量明显增加，差异有统计学意义（P〈0．05），而RPE组和APA组未见明显变化。结论微囊化人RPE细胞对PD大鼠模型有治疗作用，可作为一种前景良好的治疗PD的方法进一步研究。

Objective To observe the therapeutic effect of microencapsulated human retinal pigment epithelial （RPE） cell transplantation into the striatum in a rat model of Parkinson＇ disease （PD）. Methods Cultured RPE cells were microencapsulated by alginate-polylysine-alginate （APA） using a high voltage electrostatic system. The Parkinsonian rats were divided into 4 groups, namely the model group, RPE group, APA group and RPE-APA group, and in the latter 3 groups, RPE cells, empty APA mierocapsules and APA-capsulated RiPE cells, respectively, were transplanted into the fight striatum of the rats via stereotactie surgery. After the transplantation, the changes in apomorphine-induced rotation of the rats were investigated and the striatum DA contents were measured with high-performance liquid chromatography with electrochemical detection. Results TThe rotation of the rats in RPE-APA group was reduced by 51.48%, showing significant difference from that in the model control group 4 weeks after the transplantation （P〈0.05）. At 8 weeks after the transplantation, apomorphine-induced rotation in the RPE-APA group showed further significant reduction by 54.43% （P〈0.05）. The changes of DA contents in the striatum al%r transplantation were consistent with the changes in the rotation behavior of the rats. Conclusions Microencapsulated human RPE cell transplantation is a promising approach for the treatment of PD.