摘要
目的 观察人类神经元性芳香族氨基酸脱羧酶 (AADC)基因修饰的原代培养SD大鼠骨胳肌细胞脑内移植后对帕金森病模型鼠的治疗效果。 方法 将AADC转基因骨骼肌细胞及空骨骼肌细胞分别移植于实验组与对照组帕金森病模型鼠毁损侧纹状体 ,观察其病理性旋转行为的改善 ,并在该基础上对两组大鼠分别采用一定浓度的L dopa进行治疗 ,观察脑内移植AADC基因后对大鼠旋转行为的进一步改善。采用免疫组化方法确定AADC的表达。 结果 AADC转基因骨骼肌细胞脑内移植后 ,帕金森病模型大鼠旋转行为获得了一定的改善 (P <0 0 5 ) ,并可持续至少 15周 ;外源性L dopa治疗后旋转行为有更明显改善 ,以 11周时最为显著 ,由移植前 (10 0± 0 2 )圈 /min减少至(1 8± 0 8)圈 /min ;免疫组化证实转基因骨骼肌细胞在脑内存活可达 15周 ,以及目的基因在脑内的稳定表达。 结论 脑内植入AADC转基因骨骼肌细胞 ,增加了脑内AADC基因的表达 ,有效地改善了帕金森病大鼠的旋转行为 ,增加了L dopa治疗效果 ,有助于在低剂量L dopa维持的疗效。
Objective To observe the theraputic effect of grafting the primary cultured skeletal muscle cells modified by eukaryotic expression recombinants of aromatic-l-amino-acid decarboxylase (AADC) gene into the striatum of Parkinsonian SD rats models. Methods The gene-modified and non-modified muscle cells were grafted into the striatum of Parkinsonian SD rats of experimental and control groups respectively,and then was observed their improvement of rotational behavior. Furthermore,the effect of the combinded administration of exogenous L-dopa was evaluated. The expression of AADC was assayed by immunohistochemical staining. Results After injecting genetically modified muscle cells into the striatum,the rotational behavior of Parkinsonian rats recovered in some degree ( P <0.05),and this persisted for at least 15 weeks After coadministrating exogenous L-dopa (10 mg/kg weight) per days. the improvement of rotational behavior achieved more obviously than that in control groups ( P <0.05),and reached maximum at 11th week when the rotation frequency decreasd from (10.0 ±0.2) r/min to (1.8 ±0.8) r/min. Immunohistochemical staining showed the survival of transplanted genetically modified muscle cells and the stable expression of the target gene in the striatum. Conclusions The grafting of genetically modified muscle cells capable of producing AADC into the striatum of Parkinson ' s rats increases the expression of AADC gene in the brain which can improve the rotational behavior of Parkinsonian rats and elevates the effect of exogenous L-dopa therapy,which will be helpful to maintain a long-term theraputic effects at much lower dosage of L-dopa.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2004年第7期500-502,共3页
Chinese Journal of Geriatrics
基金
广东省自然科学基金资助项目 (编号 970 0 72 )
中山医科大学"2 11工程"重点学科资助项目 (编号 19990 3 )
