骨髓间充质干细胞黑质内移植对帕金森病大鼠的治疗作用

摘要

目的 探索骨髓间充质干细胞(BMSCs)移植到帕金森病(Parkinson's disease,PD)大鼠毁损侧黑质内,PD模型大鼠的姿势不对称性和黑质及纹状体内酪氨酸羟化酶(tyrosine hydroxylase,TH)表达的改变,以及BMSCs在大鼠脑内的存活、分化情况.方法 黑质、前脑内侧束两点法注射6-羟多巴胺(6-OHDH)并行为学分析筛选PD模型大鼠.将PD模型大鼠随机分为移植组和对照组.BMSCs移植术后4周和8周,观察大鼠姿势不对称性,免疫组织化学及免疫荧光显色方法检测黑质和纹状体酪氨酸羟化酶 (tyrosine hydroxylase,TH) 的表达变化以及BMSCs在大鼠体内的存活、迁移及分化情况.结果 BMSCs黑质内移植可使PD模型大鼠的转动频率由(10.62±2.97)r/min降至(4.65±1.08)r/min(P<0.01),显著增加毁损侧黑质TH阳性细胞数量和纹状体内TH阳性纤维密度.BMSCs在大鼠黑质内可以存活至少8周,部分细胞分化为神经干细胞、神经元和神经胶质细胞.结论 黑质内移植BMSCs对PD模型大鼠有一定的治疗作用.%Objective To explore the effect of bone marrow mesenchymal stem cells (BMSCs) transplanted into the unilateral lesioned substantia nigra (SN) , the changes of postural asymmetry and expression of tyrosine hydroxylase in SN of Parkinson's disease ( PD) model rats, and the survival and differentiation of BMSCs in the brain tissue. Methods Model of Parkinson's dieases (PD) was induced by 6-hydroxydopamine (6-OHDA) injection into the right SN and medial forebrain bundle in the rat brains. The PD rats were randomly divided into transplantation group and control group. The PD rat rotational behavior was induced by apomorphine ( APO) at 4 weeks and 8 weeks after BMSCs transplantation. The rat behavior was tested, and the expression of tyrosine hydroxylase ( TH ) and the survival, migration and differentiation of transplanted BMSCs in the SN and ST were examined using immunohistochemical and immunofluorescence-labeling staining. Results After the BMSCs transplantation, the numbers of rotation of the rats was reduced from 10. 62 ±2. 97 r/min to 4. 65 ± 1. 08 r/min ( P < 0. 01 ) , while the number of TH-positive cells in the SN and the density of TH-positive fibers in the striatum were increased significantly. The transplanted BMSCs in PD rats survived at least for 8 weeks, and a part of cells differentiated into neural stem cells, neurons and glial cells. Conclusion BMSCs transplanted into the substantia nigra of brain may have therapeutic effects on rat models of Parkinson's disease.