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目的:探讨在多巴胺水平对帕金森病进行直接转基因调控。方法应用腺伴随病毒(AAV)载体共转导酪氨酸羟化酶(TH)和芳香族氨基酸脱羧酶(AADC)基因于模型大鼠纹状体,以复合感染方式将AAVTH和AAVAADC通过立体定向法注射入帕金森病大鼠病损侧纹状体,连续观测转导后大鼠行为改善情况,并以免疫组化方法测定TH和AADC表达。结果TH和AADC基因共转导较单纯TH基因转导更明显改善大鼠行为(P<001),组织学证据表明两基因在纹状体内获有效而稳定的共表达。结论TH和AADC基因的共转导策略,对提高帕金森病基因治疗疗效有重要意义。
Objective: To investigate the direct transgenic control of Parkinson’s disease at dopamine level. Methods Adeno-associated virus (AAV) vectors were used to co-transduce tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC) genes in the striatum of the model rats. AAVTH and AAV AADC was injected into the striatum of the lesion side of Parkinson’s disease rats by stereotactic method. The behavior of the rats after the transduction was observed continuously. The expression of TH and AADC was measured by immunohistochemistry. Results The co-transduction of TH and AADC genes significantly improved the behavior of rats (P <001) compared with TH-transduced cells alone. Histological evidence indicated that both genes were efficiently and stably co-expressed in the striatum. Conclusion The co-transduction strategy of TH and AADC genes is of great significance for improving the therapeutic effect of gene therapy of Parkinson’s disease.