祛风止动方对抽动障碍小鼠神经行为学与Notch1、D2R mRNA表达的影响

作者	单位
周亚兵	上海交通大学医学院附属新华医院中医科
吴敏	上海交通大学医学院附属新华医院中医科
阎秀菊	上海交通大学医学院附属新华医院中医科
倪建俐	上海交通大学医学院附属新华医院中医科
张欣	上海交通大学医学院附属新华医院中医科
王树霞	上海交通大学医学院附属新华医院中医科
肖光华	上海交通大学医学院附属新华医院中医科

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中文摘要:

目的观察祛风止动方对头部抽动行为与Notch1和D2R mRNA表达的影响。方法利用5-羟色胺2A/C受体激动剂(±)-1-盐酸2,5-二甲氧基-4-碘苯基丙烷-2-胺盐酸盐(DOI)连续腹腔注射14d后,诱导小鼠湿狗样头部抽动模型,随机分为中药组、西药组、模型组,分别灌胃祛风止动方煎剂(10g/kg)、氟哌啶醇(1mg/kg)和蒸馏水,正常组灌胃蒸馏水,干预2周后,评价头部抽动和爬行距离,荧光实时定量PCR检测前额叶皮层和纹状体Notch1 mRNA和D2R mRNA表达。结果中药能明显改善小鼠头部抽动行为,减少爬行距离,与西药组比较差异无统计学意义(P>0.05)。纹状体D2R mRNA相对表达量明显高于额叶皮层,差异有统计学意义(P<0.01);在前额叶皮层部位,中药组、西药组D2R mRNA表达量分别为(151±30)、(180±41),明显高于模型组(P<0.05)。在纹状体部位,中药组D2R mRNA表达量分别为(710±64)、西药组(850±80),均明显高于模型组(P<0.05)。各组前额叶皮层Notch1 mRNA表达量均低于纹状体部位,差异有统计学意义(P<0.05);给药14天,中药组和西药组前额叶皮层表达下调,表达量分别(55±20)、(48±23),明显低于模型组(P<0.05)。结论DOI诱导湿狗样头部抽动能较好模拟TD临床特征,祛风止动方能明显改善小鼠抽动行为和爬行距离,复方能上调D2R mRNA表达,可能与Notch1表达下调有关联,值得进一步研究。

英文摘要:

Objective To evaluate the effect of Qufeng Zhidong Recipe (QZR) on the head tic behavior,and the mRNA expressions of Notch1 and dopamine D2 receptor (D2R) in tic disordered mice. Methods Mouse model like wet-dog shake head tic disorder was established by peritoneal injection of 5-HT2A/C agonist DOI for 14 successive days. The model mice were divided into three groups,the model group,the Chinese medicine (CM) treated group and the Western medicine (WM) treated group,they were intervened respectively with distilled water,QZR (10 g/kg) and haloperidol (1 mg/kg). Besides,a normal control group was set up and gastrogavaged with distilled water. The effect of intervention was evaluated 2 weeks later by estimating the head tic and the creeping distance of animals,and the mRNA expressions of D2R and Notch1 in corpus striatum and prefrontal cortex regions were detected using Real-time PCR. Results The wet-dog shake response and the creeping distance of mice were significantly reduced after intervention in both intervened groups,showing insignificant difference between the effects of CM and WM (P>0.05). The expression of D2R mRNA in corpus striatum was higher than that in the prefrontal cortex (P<0.01),at the prefrontal cortex,it was 151±30 in the CM group and 180±41 in the WM group,and at the corpus striatum,710±64 and 850±80 respectively,all higher than those in the model group (P<0.05). While the Notch1 mRNA expression in model mice were lower at the prefrontal cortex than at the corpus striatum (P<0.05). After intervention it was 55±20 in the CM group and 48±23 in the WM group at the prefrontal cortex,all significantly lower than that in the model group (P<0.05). Conclusion DOI-induced wet-dog shake response could well simulate the clinical characteristics of tic disorder;QZR could improve the tic behavior and creeping distance in the model mice. The up-regulation of D2R mRNA expression after QZR intervention may be related with the down-regulation of Notch1 expression,this findings is worthy of further studies.

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