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强制性运动训练对帕金森病大鼠酪氨酸羟化酶及胶质细胞源性神经营养因子表达的影响

The effects of constraint-induced movement therapy on expression of tyrosine hydroxylase and glial cell derived neurotrophic factor in Parkinson's disease model rats

摘要目的 观察强制性运动训练对帕金森病(PD)模型大鼠酪氨酸羟化酶(TH)及胶质细胞源性神经营养因子(GDNF)表达的影响.方法 共选取50只SD大鼠,采用6-羟基多巴胺(6-OHDA)单侧两点注射法制备PD动物模型,l周后将制模成功的42只大鼠随机分为运动组及对照组.运动组通过石膏固定健侧前肢,从而强制大鼠使用患侧肢体;对照组制模后未给予特殊处理.待2周训练结束后,每组大鼠腹腔注射阿朴吗啡(APO)进行行为学测试,记录30 min内转圈数量;然后处死大鼠取脑纹状体制成标本,采用高效液相-电化学法测定各组大鼠纹状体内多巴胺(DA)及其代谢物3,4-二羟基苯乙酸(DOPAC)含量;采用免疫组化技术检测各组大鼠纹状体TH及GDNF表达情况,采用逆转录-聚合酶链反应(RT-PCR)测定TH及GDNF mRNA 表达.结果 与对照组比较,运动组在APO诱导下30 min内转圈数量显著减少(P<0.05);运动组纹状体匀浆中DA及其代谢物DOPAC含量显著增加(P<0.05);运动组纹状体TH、GDNF蛋白及mRNA表达均显著强于对照组(P<0.05).结论 强制性运动训练可改善PD大鼠行为学功能,其机制可能与促进大脑纹状体TH及GDNF表达、提高DA及其代谢产物DOPAC含量有关.

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abstractsObjective To explore the effects of constraint-induced movement therapy (CIMT) on the expression of tyrosine hydroxylase (TH) and glial cell derived neurotrophic factor (GDNF) in Parkinson's disease (PD) model rats. Methods PD models were established by microinjection of 6-hydroxydopamine (6-OHDA) solution into substantia nigra of rats' right cerebral hemisphere.Forty-two model rats were divided randomly into an exercise group and a control group 1 week after microinjection.The exercise group rats were forced to use their impaired limbs by placing their nonimpaired fore-limbs in casts.The control group rats were housed in the same environment without any special treatment.Two weeks after 6-OHDA infusion and exercise training,the behavioral changes of rats were examined after intraperitoneal injection apomorphine ( APO).The content of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) was measured by high performance liquid chromatography with electrochemistry ( HPLAEC) ; the expressions of TH and GDNF in striatum were detected by immunohistochemical methods and TH,GDNF mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results After 2 weeks of training,the rotating laps of the rats in exercise group within 30 min after APO induction,reduced to a significantly greater extent when compared to the control group (P < 0.05).The content of DA and it's metabolites DOPAC in striatum homogenate was significantly higher in exercise group than that in the control group ( P < 0.05 ),and the expression levels,of TH and GDNF protein/ mRNA were also significantly higher in the exercise group than those in control group ( P < 0.05 ). Conclusions CIMT can improve the behavioral performance of PD rats,probably through promoting the expressions of TH and GDNF protein/mRNA in striatum,and increasing DA and it's metabolites DOPAC level.

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