帕金森病大鼠TH和AADC基因的共转导研究

Co-transfer of tyrosine hydroxylase and aromatic amino-acid decarboxylase cDNAs into the denervated striata of Parkinsonian rats

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ＡＡＶＴＨ和ＡＡＶＡＡＤＣ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＜００１），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 Explore the possibility of directly transgenic regulation of Parkinson's disease at dopamine synthesis level.Method AAVTH and AAVAADC were stereotaxically coinjected into the denervated striatum of Parkinsonian rat; apomorphineinduced rotational behavior and the immunohistochemistry of TH and AADC were analysed. Result A better behavious recovery was shown in the rats coinjected with AAVTH/AAVAADC than those with AAVTH alone. The immunostaining showed that TH and AADC were coexpressed efficiently in the striatum.Conclusion Cotransfer of TH and AADC cDNAs into the striatum is a valuable strategy to gene therapy for Parkinson's disease.