左旋多巴诱发异动症6-羟基多巴帕金森病大鼠模型的建立及行为学评价

Establishment and Evaluation of the Behavior of the Parkinson′s Disease Rat Model of Levodopa Induced Dyskinesias

目的应用左旋多巴(L-DOPA)建立帕金森病(PD)大鼠异动症模型,对其行为学进行评价。方法对25只SD大鼠右内侧前脑束注射6-羟基多巴(6-OHDA)建立PD大鼠模型,两周后行阿朴吗啡(1mg/kg)皮下注射,将成功PD大鼠模型随机分成两组,分别予生理盐水(NS)45mg/kg和L-DOPA(25mg/kg+6.25mg/kg苄丝肼)腹腔注射,2次/d,共治疗21d,在治疗第2、9、11、18、21d进行前肢功能测定、异常不自主运动(AIM)评分和旋转反应时间测定。结果 20只建模成功的PD大鼠模型中,10只给以生理盐水(NS)治疗,另10只给以L-DOPA治疗。NS组治疗前后前肢跨步数无明显差异(P>0.05),治疗期间始终未出现AIM;L-DOPA治疗组后前肢跨步数较治疗前显著增加(P<0.01),8只出现不同程度的AIM表现,并随治疗时间的延长,AIM评分逐渐升高,第21dAIM总分较第2d增加(P<0.05),旋转反应时间随治疗时间的延长而缩短,第18、21d和第2d相比,显著缩短(P<0.05)。结论 L-DOPA诱发6-OHDA的PD大鼠AIM与PD患者服用美多巴出现的异动症某些方面相似,为研究异动症提供了理想的模型。

Objective To establish the Parkinson’s disease （PD） rat model of the levodopa induced dyskinesia （LID） with the application of L-DOPA and 6-OHDA and to evaluate their behavioral characteristics.Methods The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to right medial forebrain bundle （MFB）.Two weeks later,apomorphine-induced rotation test was performed to examine the rat model of PD.Animals were intraperitoneally treated by NS（45mg/kg） and L-DOPA （25mg/kg＋6.25 mg/kg benserazide） respectively twice daily for 21 days.On the 2nd day,9th day,11th day,18th day,the 21st day during the treatment,forepaw adjusting steps and AIM and rotational duration were respectively observed.The quality of AIM was estimated by using the rat AIM rating scale.Results Twenty successful rat PD models,ten of whom were given NS treatment,while the other ten L-DOPA treatment.Contralateral forepaw performance was significantly improved after levodopa treatment,not NS treatment,but gradually reduced with more and more severe AIM following repeated levodopa therapy.The treatment of levodopa gradually induced abnormal involuntary movement（AIM） and the score of AIM gradually increased.Rotation duration was shortened significantly.On the 21st day,the AIM Score increased compared to the 2nd day.Rotation duration was shortened significantly.Conclusion Levodopa·induced rat AIM model of PD is similar to that with the levodopa-induced dyskinesia （LID） in PD patients,which provides an ideal model for LID study.