摘要
目的探讨长期左旋多巴作用对帕金森病(PD)运动并发症模型大鼠纹状体神经元N-甲基-D-天冬氨酸(NMDA)受体亚型1(NR1)特性的影响。方法建立PD运动并发症大鼠模型(n=25),并随机分为三组。左旋多巴长期处理组(n=10):腹腔注射左旋多巴甲酯23 d;MK-801处理组(n=10):第23天左旋多巴甲酯注射前腹腔注射MK-801;溶剂处理组(n=5):腹腔注射0.2%维生素C液。另设假手术组(n=5)为对照组。观察MK-801处理组大鼠行为学变化;采用Western blotting检测另三组大鼠纹状体膜蛋白NR1磷酸化情况。结果MK-801处理组大鼠在左旋多巴应用第1、8、15、22天,呈现旋转反应时间逐渐缩短及剂峰旋转次数递增的趋势;第23天应用MK-801后,剂峰旋转次数与第22天相比明显减少(P<0.05),旋转反应时间则明显延长(P<0.05)。与假手术组相比,溶剂处理组膜蛋白中NR1、磷酸化NR1S890和NR1S896的表达量均下降(P<0.05);而两组磷酸化NR1S897的表达量比较,差异无统计学意义(P>0.05)。与溶剂处理组相比,左旋多巴长期处理组NR1及磷酸化NR1S890、NR1S896和NR1S897在膜蛋白中的表达量均升高(P<0.05)。结论左旋多巴引起的PD大鼠运动反应变化可能与NR1的特性改变有关。
Objective To explore the effects of chronic levodopa treatment on characteristics of N-methyl-D-aspartate （NMDA） receptor subunit 1 （NR1） on the neurons of striatum in rat models of Parkinsonism related motor complications. Methods Rat models（ n = 25） of Parkinsonism related motor complications were established and were randomly divided into solvent treatment group （ n = 5, intraperitoneal injection with vitamin C）, levodopa chronic treatment group （ n = 10, intraperitoneal injection with levodopa for 23 d） and MK-801 treatment group（n = 10, intraperitoneal injection with MK-801 on d 23 after intraperitoneal injection with levodopa for 22 d）. Another 5 rats were served as controls （sham-operation group, n = 5）. Locomotion changes of rats in MK-801 treatment group were recorded, and NR1 phosphorylation in the other three groups was detected by Western blotting. Results After chronic treatment with levodopa methylester for 1, 8, 15 and 22 d, rats in MK-801 treatment group displayed shortened rotational duration and increased peak rotation. Compared with d 22, MK-801 both prolonged rotational duration and reduced peak rotation （P 〈 0.05）. Compared with sham-operation group, the expression of NR1 and phosphorylated NR1 S890 and NR1 S896 in striatal membrane fractions in solvent treatment group was reduced（P 〈 0.05）, while there was no significant difference in the expression of NR1S897 （P 〉 0.05）. The expression of NR1, phosphorylated NR1 S890, NR1 S896 and NRIS897 in striatal membranes in levodopa chronic treatment group was increased compared with that of solvent treatment group （ P 〈 0.05）. Conclusion Alterations of locomotion response caused by levodopa may correlate with characteristics of NR1.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2009年第5期535-538,共4页
Journal of Shanghai Jiao tong University:Medical Science
基金
上海市浦江人才计划(PJ[2007]00346)
上海市科委基金(07SP07005)~~
