左旋多巴对帕金森病大鼠纹状体多巴胺转运体的影响

摘要

目的 研究左旋多巴(L-dihydroxy-phenylalanine,LD)对帕金森病大鼠纹状体多巴胺转运体的影响.方法 采用脑部偏侧注射6-羟基多巴胺(6-hydroxydopamine,6-OHDA)制备PD模型,并将成功模型随机分为PD模型组、LD治疗组,并以正常大鼠作对照,每组9只.其中LD治疗组大鼠给予腹腔注射左旋多巴/苄丝肼 (50mg/kg左旋多巴和12.5mg/kg苄丝肼即左旋多巴和苄丝肼溶于含0.05%的乙醇和0.1%的抗坏血酸的注射用水中,配成10mg/ml),每日两次;PD模型组及正常对照组给予腹腔注射等量的含0.05%的乙醇和0.1%的抗坏血酸的注射用水,每日两次.分别于4、6、8周,每组各取3只大鼠,行脑纹状体内多巴胺转运体125I-β-CIT放射自显影,同时用γ-计数器测定纹状体内多巴胺转运体放射活性,计算每克纹状体含放射性占注射剂量的百分比(%ID/g).结果 损毁侧在不同时间段,与正常对照组比较,PD模型组、LD治疗组DAT数量均明显降低,差异均有统计学意义(P<0.01);LD治疗组随时间的延长,呈现递减趋势,但差异尚无统计学意义(P>0.05).健侧在6周时与正常对照组比较,PD模型组及LD治疗组DAT数量降低,差异有统计学意义(P<0.05);LD治疗组DAT数量有递减趋势,但差异无统计学意义(P>0.05).纹状体自显影结果 与纹状体内标志物放射活度测定结果 基本一致.结论 长期每日应用50mg/kg LD治疗PD模型大鼠可能会使纹状体内多巴胺转运体的数量减少.%Objective To atudy the effects of levodopa ( L - dihydroxy - phenylalanine) on DAT ( dopamine transporter) in rats striatum with Parkinson's disease. Methods The PD model rats were prepared by injection of 6 - OHAD (6 - hydroxydopamine) in lateral brain. The successful models of PD were randomly divided into the PD model group and LD treatment group, with normal rats as control (n =9). The rats in LD treatment group were given intraperitoneal injection of levodopa / benserazide (50mg/kg of levodopa and 12. 5mg/kg of benserazide,i e. levodopa and benserazide being soluble in water for injection containing 0. 05％ ethanol and 0. 1％ ascorbic acid and prepared in 10mg/ml) , Bid. The rats in PD model group and nomal control group were given intraperitoneal injection of equal amount of water containing 0. 05 ％ ethanol and 0.1％ ascorbic acid, twice daily. Three rats from each group were selected and their DAT in atriatum were dealt with 125I- β - CIT autoradiography in 4th, 6th and 8th weeks. Meanwhile , radioactivity of DAT in striatum was determined with γ - counter and the percentage of radioactivity in each gram of striatum versus total injection dose ( ％ ID/g) waa calculat ed. Results Compared with the normal control group during different phases, the number of DAT of the damaged part in PD model group and LD treatment group were significantly decreased (P ＜0.01). As time going, the number of DAT in the LD treatment group tended to decrease with no significant statistical difference ( P ＞ 0. 05 ) . Compared with the nomal control group at the 6th week , the number of DAT in the normal part in PD model group and LD treatment group were significantly decreased (P ＜0. 05). While the number of DAT in LD treatment group was decreased , but the difference showed no significance ( P ＞ 0. 05 ) . The results from autoradiography and marked radioactivity test in striatum were basically identical. Conclusion The number of DAT in PD model rats' striatum may be reduced by longterm use of LD in 50mg/kg per day.