cAMP应答元件结合蛋白在左旋多巴诱发异动症大鼠发病机制中的作用  

Effect of Antisense CREB on the Expression of Prodynorphin Gene in Rats with Levodopa Induced Dyskinesis

作　　者：孙斌 陈广新 张瑛玉 苏崇一[3] 司毅 

机构地区：[1]山东省淄博市第三人民医院 [2]山东省淄博市中心医院 [3]山东省立医院

出　　处：《中西医结合心脑血管病杂志》2006年第4期313-315,共3页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的探讨纹状体内注射转录调控因子cAMP应答元件结合蛋白(CREB)基因对左旋多巴诱发异动症(LID)帕金森病大鼠前强啡肽原基因表达的影响。方法6-羟基多巴胺(6-OHDA)立体定位注射制备偏侧帕金森病大鼠模型,左旋多巴腹腔注射治疗4周诱发LID大鼠模型。向各大鼠模型纹状体内分别注射1μL的反义、正义CREB,进行异常不自主运动(AIM)功能评分,并采用原位杂交方法观察大鼠纹状体内前强啡肽原基因的变化。结果正常大鼠纹状体内注射反义CREB后前强啡肽原mRNA水平明显增加(P<0.01),LID大鼠给予正义、反义CREB治疗后,AIM评分与前强啡肽原mRNA水平均无明显变化(P>0.05)。结论在LID大鼠中,CREB失去了正常的前强啡肽原mRNA调控功能,是发生LID的关键因素之一。Objective To explore the effects antisense,sense response element binding protein （CREB） on the expression of prodynorphin（PDyn） gene in striatal neurons of levodopa- induced dyskinesias （LID） rats with Parkinson disease （PD）, Methods PD rats were established by 60HDA microinjection stereotaxically. They were treated with chronic intermittent Levodopa celiac injection for 28 days to get the LID rats. Antisense, sense CREB （1μL）were injected into striatum of all rats. Hybridization in situ was used to measure the changes in the expressions of PDyn mRNA in striatum and behavior changes were observed. Results The level of PDyn mRNA increased significantly after administration of antisense CREB in control rats（P〈 0.01 ）. AIM score and level of PDyn mRaNA had no changed after administration of sense and anti- sense CREB in LID rats, Concision CREB, which regulate the CREB the expression of PDyn mRNA in control rats, had no effect on the level of PDyn mRNA in LID rats.

关 键 词：左旋多巴诱发异动症 帕金森 病 反义寡核苷酸 前强啡肽原 

分 类 号：R363[医药卫生—病理学]