反义FosB和反义CREB基因抑制左旋多巴诱发异动症大鼠前强啡肽原基因的表达  

Effects of antisense FosB and CREB protein on expression of prodynorphin gene in rats with levodopa-induced dyskinesias

作　　者：管强[1] 曹学兵[1] 徐岩[1] 王岚[1] 孙圣刚[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,武汉430022

出　　处：《中华神经科杂志》2006年第1期48-51,共4页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目(30300114)

摘　　要：目的探讨纹状体内转录调控因子FosB基因和环-磷酸腺苷应答元件结合蛋白(CREB)基因对左旋多巴诱发异动症(LID)大鼠前强啡肽原(PDyn)基因表达的影响。方法6-羟基多巴(6-OHDA)立体定位注射及慢性左旋多巴(L-dopa)治疗诱发LID大鼠模型,所有大鼠共分为对照组(n=10)、对照+反义FosB组(n=12)、对照+正义FosB组(n=13)、对照+反义CREB组(n=11)、对照+正义CREB组(n=13)、LID组(n=10)、LID+反义FosB组(n=9)、LID+正义FosB组(n=7)、LID+反义CREB组(n=8)、LID+正义CREB组(n=8)。对照组与LID组分别注射PBS,其余各组大鼠纹状体内分别注射相应反义、正义FosB和CREB。后4组大鼠进行异常不自主运动(AIM)评分,并采用原位杂交方法观察大鼠纹状体内PDyn mRNA的变化。结果反义FosB治疗前后LID大鼠AIM评分分别为40.1±9.2、12.5±5.4,差异有统计学意义(P<0.01)。LID+反义FosB组损毁侧纹状体PDyn mRNA水平(吸光度,0.2415±0.0220)较LID+正义FosB组损毁侧(吸光度,0.4105±0.0386)显著降低(P<0.01)。对照+CREB组大鼠损毁侧纹状体PDyn mRNA水平(吸光度,0.1775±0.0246)较对照组(吸光度,0.2403±0.0323)明显降低(P<0.01)。反义CREB治疗前后LID大鼠AIM评分分别为40.5±10.0、43.2±11.8,差异无统计学意义(P>0.05)。LID+反义CREB组损毁侧纹状体PDyn mRNA水平(吸光度,0.2415±0.0220)与LID+正义CREB组(吸光度,0.4087±0.0440)之间差异无统计学意义(P>0.05)。结论在LID大鼠中,FosB蛋白取代了CREB调控PDyn mRNA的表达,是发生LID的关键因素之一。Objective To explore the effects of antisense, sense FosB and response elementbinding protein （CREB） injected respectively into intra-striatum, on expression of prodynorphin （PDyn） gene in striatal neurons of levodopa-induced dyskinesias （ LID ） rats with Parkinson＇ s disease （ PD ）. Methods LID rats were established as models by 6-hydroxydopamine （6-OHDA） microinjection stereotaxical and chronic intermittent L-3,4- dihydroxyphenylalanine methyl ester （L-dopa） celiac injection. All rats were divided into control group （n = 10）, control ＋ antisense FosB group （n = 12 ）, control ＋ sense FosB group （n = 13） , control ＋ antisense CREB group （n = 11 ）, control ＋ sense CREB group （n =13） , LID group （n =10）, LID ＋ antisense FosB group （n=9）, LID ＋ sense FosB group （n =7）, LID ＋ antisense CREB （ n = 8） group and LID ＋ sense CREB group （ n = 8）. Antisense FosB and CREB, sense FosB and CREB were injected into striatum of rats respectively. Hybridization in situ was used to measure the changes in expression of PDyn mRNA in striatum and the behavior changes were observed. Results After administration of antisense FosB, scores of abnormal involuntary movement （AIM） was decreased in LID rats （ 12. 5 ± 5.4 vs 40. 1 ± 9.2,P 〈 0.01 ）. As compared with LID ＋ sense FosB group,expression of PDyn mRNA on lesioned side of striatum was decreased in LID ＋ antisense FosB group （0. 2415±0. 0220 vs 0. 4105±0. 0386, P 〈0. 01 ）. As compared with control group, expression of PDyn mRNA on lesioned side of striatum was decreased in control ＋ antisense CREB group （0. 1775±0. 0246 vs 0. 2403 ± 0. 0323, P 〈 0. 01 ）. After administration of antisense CREB, LID rats showed no changes in scores of AIM （43.2 ± 11.8 vs 40. 5 ± 10. 0, P 〉 0. 05 ）. And compared with sense CREB treated LID group, antisense CREB treated LID group also showed no changes in the expression of PDyn mRNA （0. 3930 ± 0. 0332 vs 0. 4087 ± 0. 0440, P 〉

关 键 词：运动障碍 药物性 帕金森病 原癌基因蛋白质C-FOS DNA结合蛋白质 环 AMP反应性 脑啡肽类 蛋白质前体 

分 类 号：R363[医药卫生—病理学]