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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 an animal model of Parkinson’s disease (PD) dyskinesia by levodopa (L-DOPA) and evaluate its behavior. Methods PD rats were injected with 6-hydroxydopamine (6-OHDA) into the right medial forebrain of 25 SD rats. Subcutaneous injection of apomorphine (1 mg / kg) two weeks later, the rats were randomly divided into The rats in two groups were injected intraperitoneally with saline (NS) 45 mg / kg and L-DOPA (25 mg / kg + 6.25 mg / kg benserazide) twice a day for 21 days. The forelimb function test, abnormal involuntary movement (AIM) score and rotation reaction time were measured on 18 and 21 days. Results Twenty of the 20 model rats successfully established with PD were treated with NS and 10 with L-DOPA. There was no significant difference in the number of forelimb strides between NS group before and after treatment (P> 0.05), and no AIM was observed during the treatment. The number of stride of forelimb in L-DOPA group was significantly increased (P <0.01) The AIM score gradually increased with the prolongation of treatment time, the total score of AIM increased on the 21st day (P <0.05), and the rotation reaction time shortened with the prolongation of treatment time. On the 18th, 21st, and 2d (P <0.05). Conclusions AIM of PD-induced 6-OHDA in L-DOPA is similar to that of PD in patients taking PD with metoprolol and provides an ideal model for the study of dyskinesia.