异钩藤碱对多发性抽动症模型大鼠头部抽动行为与脑内单胺递质水平的影响

Effect of isorhynchophylline on head-shakes behavior and levels of monoamine neurotransmitter in model rats with Tourette syndrome

目的 探讨钩藤碱、异钩藤碱对多发性抽动症（tourette syndrome,TS）大鼠头部抽动行为及脑内单胺递质水平的影响.方法 将40只Wistar大鼠随机分为2,5-二甲氧基-4-碘苯基丙烷（DOI）诱导的大鼠头部抽动组（HSR组）、氟哌啶醇组、钩藤碱组、异钩藤碱组,每组10只.通过行为学观察钩藤碱、异钩藤碱对大鼠抽动行为的抑制作用;应用酶联免疫吸附实验检测脑纹状体多巴胺和5-羟色胺变化;采用实时定量PCR检测前额叶皮层5-羟色胺2A受体mRNA水平.结果 与HSR组比较,异钩藤碱组和氟哌啶醇组大鼠的头部抽动次数明显减少,差异有统计学意义（均P＜0.01）,钩藤碱组大鼠头部抽动次数没有明显变化,差异无统计学意义（P＞0.05）;异钩藤碱组和氟哌啶醇组大鼠的头部抽动次数相比,差异无统计学意义（P＞0.05）.与HSR组比较,异钩藤碱组和氟哌啶醇组大鼠纹状体多巴胺水平降低[（152.35±5.80） μg/L vs（111.19±4.30） μg/L）,（152.35±5.80） μg/L vs（126.66±3.17） μg/L）,P＜0.01],钩藤碱组大鼠纹状体多巴胺水平差异无统计学意义[（152.35±5.80）μg/Lvs（142.71±5.51） μg/L）,P＞0.05];各组大鼠前额叶皮层的5-HT2A受体mRNA表达差异无统计学意义（P＞0.05）.结论 异钩藤碱能够抑制DOI诱导的大鼠抽动行为;异钩藤碱能够降低DOI诱导的头部抽动大鼠纹状体多巴胺水平;钩藤碱对大鼠抽动行为和大鼠纹状体多巴胺含量均没有明显抑制作用.

Objective To explore the effect of rhynchophylline and isorhynchophylline on headshakes behavior and levels of monoamine neurotransmitter in model rats with Tourette syndrome.Methods 40 Wistar rats were randomly divided into DOI-induced head-shakes rats （HSR group）,haloperidol group,rhynchophylline group and isorhynchophylline group with 10 in each group.The inhibitory effects of rhynchophylline and isorhynchophylline were estimated by observing the HSR behavior.Dopamine （DA） and 5-hydroxytryptamine（5-HT） in the rat striatum were detected by the enzyme-linked immunosorbent assay （ELISA） method.The 5-HT2A receptor mRNA expression in prefrontal lobe cortex of the rats was measured by real-time PCR.Results Compared with HSR group,the head shakes of the rats in haloperidol group and isorhynchophylline group were significantly decreased（P＜0.01）,and no change of head-shakes number was observed in rhynchophylline group （P＞0.05）.There was no significant difference of head-shakes number between the haloperidol group and isorhynchophylline group（P＞0.05）.Compared with HSR group,DA levels in the rat striatum were significantly decreased in isorhynchophylline group and haloperidol group（（152.35± 5.80） μ~L vs （111.19±4.30） μg/L,（152.35±5.80） μg/L vs （126.42±3.17） μg/L,P＜0.01）,while DA levels in the rat striatum in rhynchophylline group were not changed （（152.35±5.80） μg/L vs （142.71±5.51） μg/L,P＞0.05）.There was no significant change of 5-HT2A receptor mRNA expression in rat prefrontal lobe cortex in every group（P＞0.05）.Conclusion Isorhynchophylline may have an inhibitory effect on rats with DOI-induced HSR.Isorhynchophylline may decrease the DA levels in the rat stratum with DOI-induced HSR.Rhynchophylline has no significant inhibitory effect on head-shakes behavior and DA levels in the rat stratum with DOI-induced HSR.