GDNF、TGF-β1联合治疗帕金森病的实验研究  

An experimental study on the effects of GDNF and TGF-β co-transfection gene therapy in a rat Parkinson's model

作　　者：孙兵[1] 惠国桢[1] 刘相名[1] 林波[2] 余路阳[2] 郭礼和[2] 

机构地区：[1]苏州大学附一院神经外科,215006 [2]中国科学院上海生物化学与细胞生物学研究所

出　　处：《中华神经外科杂志》2004年第4期288-290,共3页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金资助项目(30271325);江苏省自然科学基金资助项目(BK2001170)

摘　　要：目的采用阳离子脂质体介导的方法,探讨胶质细胞源性神经生长因子(GDNF)、转化生长因子-β1(TGF-β1)基因联合治疗对帕金森病(PD)的疗效和两者的相互影响。方法用6-羟基多巴(6-OHDA)破坏SD大鼠一侧黑质,建立帕金森病模型,并分为对照组、GDNF治疗组、GDNF+TGF-β1治疗组。通过立体定向仪将DOTAP脂质体包裹的GDNFcDNA、TGF-β1cDNA注入大鼠的纹状体,观察阿朴吗啡(APO)诱导的旋转行为,应用RT-PCR、Westernblot分别从mRNA和蛋白水平检测GDNF在脑内表达的变化。结果治疗2周后,PD大鼠旋转行为明显减轻(P<0.01)。治疗后4周,GDNF+TGF-β1组症状进一步减轻,而GDNF组没有继续改善。RT-PCR、Westernblot显示,与GDNF组相比,联合治疗组GDNF在mRNA、蛋白水平均有较高的表达。结论阳离子脂质体介导GDNF、TGF-β1能改善帕金森病症状,TGF-β1是GDNF重要的联合因子。Objectives To investigate the effects of GDNF and TGF-β1 co-transfection gene therapy on Parkinson's disease and mutual influence of GDNF and TGF-β1. Methods 6-hydroxydopamine was stereotaxically injected into the lateral substantia nigra to establish Parkinson's disease model. Following the intrastratial grafts of liposome encapsulated GDNFcDNA and TGF-β1cDNA, therapeutic effects were evaluated by observing the apomorphine-induced rotation. Expression of GDNFcDNA was assayed with RT-PCR and Western blot 4 weeks after therapy. Results 2 weeks after grafts, the rotations of therapeutic group decreased significantly(P<0.01). Compared with GDNF group, behavioral recovery was maintained in GDNF and TGF-β1 group till 4 weeks(P<0.01), meanwhile, expression of GDNF elevated on both mRNA and protein level. Conclusion Catonic liposome mediated GDNF and TGF-β1 can effectively improve symptoms of Parkinson's disease. TGF-β1 is an important cofactor of GDNF to elevate its trophic actions.

关 键 词：GDNF TGF-Β1 联合治疗 帕金森病 实验研究 

分 类 号：R742.5[医药卫生—神经病学与精神病学]