长期应用不同剂量左旋多巴对帕金森病大鼠模型学习记忆能力和同型半胱氨酸的影响

The effects on learning and memory capacity,the plasma levels of homocysteine by using Levodopa of the long term and different dose in Parkinson disease rat

目的观察长期应用不同剂量左旋多巴(L-dopa)对帕金森病(PD)模型大鼠的学习记忆能力和同型半胱氨酸的影响。方法应用6-羟多巴胺制作PD大鼠模型。将288只成功PD模型大鼠分为两组(对照组,实验组)。实验组(三小组)分别用不同剂量的L-dopa(10mg.kg-1.d-1,20mg.kg-1.d-1,30mg.kg-1.d-1)腹腔注射,连续28d,分别于不同时点(1d、3d、5d、7d,14d和28d)作行为学测定;抽血测定同型半胱氨酸、叶酸。同时分离大鼠海马区制作冰冻切片,左侧海马进行刚果红染色并测定海马区β淀粉样蛋白阳性斑块的积分吸光度,右侧海马测定大鼠海马区乙酰胆碱酯酶(AChE)活力。结果随着应用L-dopa剂量的增大,时间的增加可使PD模型大鼠:(1)学习记忆能力明显下降(P<0.001);(2)血浆同型半胱氨酸浓度升高,叶酸浓度降低(P<0.001);(3)海马区β淀粉样蛋白阳性斑块增多(P<0.05);(4)降低大鼠海马区AChE活力(P<0.001)。结论长期大量使用L-dopa能使PD模型大鼠学习记忆能力明显下降,血浆同型半胱氨酸浓度升高,引起β淀粉样蛋白阳性斑块增多,海马区AChE活力下降,推测长期大量使用L-dopa导致的帕金森病痴呆(PDD)可能与同型半胱氨酸升高有关。

Objective To observe the effects on learning and memory capacity,the plasma levels of homocysteine by using levodopa of the long term and different dose in Parkinson Disease rat.Methods The model rats for PD were established through 6-OHDA.The success 288 model rats were randomly divided into 2 groups： control group（CG）,Levodopa group（LG）.In addition,the LG group was divided into 3 subgroups,Levodopa（L-dopa）（10mg.kg-1.d-1,20mg.kg-1.d-1,30mg.kg-1.d-1） was respectively administered intraperitoneally to each subgroup of rats for 28 consecutive days.At different time（1st day,3rd day,5th day,7th day,14th day,28th day）,we observed the rats＇ behavioral change and tested plasma levels of Homocysteine and Folic Acid.Preparations of left hippocampus were stained with Congo red,and β protein deposit of hippocampus were analysised by integral absorbance（IA）.And right hippocampus were checked activity of acetylcholinesterase（AChE）.Results （1） The learning and memory capacity of Parkinson disease rat was significantly degraded in coincidence with the doses and the time of Levodopa（P0.001）.（2） The plasma levels of Homocysteine showed significantly increasing and levels of Folic Acid showed significantly decreasing in coincidence with the doses and the time of Levodopa（P0.001）.（3） The β protein deposit in hippocampus was also increased in coincidence with the doses and the time of Levodopa（P0.05）.（4） The AChE activity in hippocampus was decreased in coincidence with the doses of Levodopa（P0.001）.Conclusions The long term and large dose usage of Levodopa may degrade the learning and memory capacity and the plasma levels of Homocysteine was increased,increase the β protein deposit in hippocampus of Parkinson disease rat.But the AChE activity in hippocampus was decreased in coincidence with the doses of Levodopa（P0.001）.These observations suggest that,from the PD to the PDD,is correlated with increasing of plasma levels of Homocysteine.