帕金森病大鼠模型学习记忆能力与左旋多巴的关系  

Relationship between learning and memory capacities and levodopa in rat models of Parkinson's disease

作　　者：邢红霞[1] 袁燕[1] 刘胜[2] 殷闯[3] 韩金红[4] 周慧聪[5] 苏洲[1] 郭双喜[1] 王玉梅[1] 

机构地区：[1]新乡医学院第一附属医院神经内一科,河南省卫辉市453100 [2]新乡医学院第一附属医院新普外二科,河南省卫辉市453100 [3]新乡医学院第三附属医院神经内科,河南省新乡市453003 [4]新乡医学院基础医学院组织与胚胎教研室,河南省新乡市453003 [5]新乡医学院第一附属医院消化内科,河南省卫辉市453100

出　　处：《中国组织工程研究》2014年第7期1069-1075,共7页Chinese Journal of Tissue Engineering Research

基　　金：2006年新乡医学院立项资助项目~~

摘　　要：背景:帕金森病治疗的经典药物是左旋多巴,但是长期应用会产生异动症等并发症。目的:观察左旋多巴对帕金森病模型大鼠学习记忆能力的影响,并探讨其机制。方法:应用6-羟多巴胺制作帕金森病大鼠模型。将228只造模成功的帕金森病大鼠分为对照组和实验组,实验组大鼠分别按10,20,30 mg/(kg·d)腹腔注射左旋多巴,连续28 d,然后分别于腹腔注射后1,3,5,7,14,28 d测定其学习记忆能力及血浆同型半胱氨酸和叶酸水平。测定大鼠海马区乙酰胆碱酯酶活性,并应用Bielschowsky染色观察海马神经原纤维缠结。结果与结论:随左旋多巴剂量增大、应用时间延长,可明显降低大鼠学习记忆能力(P<0.001);升高血浆同型半胱氨酸水平,降低叶酸水平(P<0.001);降低大鼠海马区乙酰胆碱酯酶活性(P<0.001);增多大鼠海马区神经原纤维缠结(P=0.000)。提示大量使用左旋多巴可造成帕金森病模型大鼠学习记忆能力明显下降,引起海马区乙酰胆碱酯酶活性下降,促进海马区神经原纤维缠结增多,其机制可能与升高同型半胱氨酸有关。BACKGROUND：Classical drug for Parkinson’s disease is levodopa, but long-term application of levodopa can induce complications such as dyskinesias. OBJECTIVE：To observe the effects of levodopa on learning and memory capacities of Parkinson’s disease rats and to study its mechanisms. METHODS：The rat models of Parkinson’s disease were established using 6-hydroxydopamine. The 228 model rats were randomly divided into control group and experimental group. Rats in the experimental group were intraperitoneal y injected with 10, 20 and 30 mg/（kg？d） levodopa for 28 consecutive days. At 1, 3, 5, 7, 14 and 28 days after intraperitoneal injection, we observed the rats’ learning and memory capacities and tested plasma＆nbsp;concentration of homocysteine and folic acid. Acetylcholinesterase activities in the rat hippocampus were measured. Hippocampal neurofibril ary tangles were observed using Bielschowsky staining. RESULTS AND CONCLUSION：Increased dose of levodopa and prolonged application time obviously decreased learning and memory capacities in rats （P〈0.001）, increased plasma homocysteine levels, reduced folic acid levels （P〈0.001）, diminished acetylcholine esterase activities in the rat hippocampus （P〈0.001）, and increased neurofibril ary tangles in the rat hippocampus （P=0.000）. Results suggested that a large dose of levodopa could significantly decrease the learning and memory capacities, and disease acetylcholine esterase activities, and increase neurofibril ary tangles in hippocampus. Its mechanism possibly associated with the increased plasma concentration of homocysteine.

关 键 词：组织构建 组织工程 左旋多巴 帕金森病 学习记忆 乙酰胆碱酯酶 神经原纤维缠结 同型半胱氨酸 大鼠 

分 类 号：R318[医药卫生—生物医学工程]