CAJ | 학술논문

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。
배경：파금삼병치료적경전약물시좌선다파，단시장기응용회산생이동증등병발증。 　　목적：관찰좌선다파대파금삼병모형대서학습기억능력적영향，병탐토기궤제。 　　방법：응용6-간다파알제작파금삼병대서모형。장228지조모성공적파금삼병대서분위대조조화실험조，실험조대서분별안10，20，30 mg/(kg?d)복강주사좌선다파，련속28 d，연후분별우복강주사후1，3，5，7，14，28 d측정기학습기억능력급혈장동형반광안산화협산수평。측정대서해마구을선담감지매활성，병응용Bielschowsky염색관찰해마신경원섬유전결。 　　결과여결론：수좌선다파제량증대、응용시간연장，가명현강저대서학습기억능력(P <0.001)；승고혈장동형반광안산수평，강저협산수평(P <0.001)；강저대서해마구을선담감지매활성(P <0.001)；증다대서해마구신경원섬유전결(P=0.000)。제시대량사용좌선다파가조성파금삼병모형대서학습기억능력명현하강，인기해마구을선담감지매활성하강，촉진해마구신경원섬유전결증다，기궤제가능여승고동형반광안산유관。
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 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.