运动疲劳引起纹状体突触超微结构变化及D2DR介导的行为学干预研究

Exercise-induced Fatigue Influenced Striatal Neuron's Synaptic Ultrastructure and D2DR Intervention Role in Rat

目的:观察运动疲劳后大鼠纹状体背外侧部(DLS)突触超微结构变化及D2DR干预对大鼠自主活动能力的影响,探讨黑质-纹状体通路在运动疲劳中枢调控中的作用。方法:Wistar大鼠建立运动疲劳模型,分为对照组(CG)、一次性力竭运动组(1FG)、3 d重复力竭组(3FG)、7 d力竭运动即刻组(7FG)、7 d力竭运动24 h恢复组(24RG)和7 d力竭运动48 h恢复组(48RG)。采用透射电子显微镜观察DLS突触超微结构变化,免疫组化检测PSD-95蛋白表达情况,并对其与超微结构相关性进行分析;采用D2DR拮抗剂、激动剂干预大鼠自主运动能力,对其旷场行为进行分析。结果:1)与CG组相比,1FG组DLS突触间隙显著减小(P<0.01),3FG和7FG组较CG和1FG组致密物厚度显著减小(P<0.05);2)24RG组PSD-95蛋白表达较CG和1FG组显著增加(P<0.05);3)各组大鼠运动总距离随运动强度增加而减少,且可恢复至安静水平。注射D2DR拮抗剂后力竭时间显著缩短(P<0.01),而激动剂干预后力竭时间显著增加(P<0.01)。结论:PSD厚度随着运动疲劳程度加深逐渐减小;运动疲劳影响PSD-95蛋白表达,但其与运动疲劳程度没有相关性;运动疲劳使大鼠自主活动能力降低,D2DR拮抗剂干预加深这一作用,而D2DR激动剂可缓解大鼠活动能力的降低,提示,D2DR的调节作用与黑质-纹状体DA能微环路突触可塑性有关,D2DR可作为改善运动疲劳的靶点。

Objective： Through investigating dorsolateral striatum （DLS） synaptic ultrastmctural change and D2DR antagonist/agonist effect on autonomic activity in exercise-induced fatigue rats, explore the central regulation role of substantia nigra striatum pathway. Methodology： Male Wistar rats were randomly divided into control group （CG）, 1-day fatigue group （1FG）, 3-day fatigue group （3FG）, 7-day fatigue group （7FG）, 24-hour recovery group （24RG） and 48-hour recovery group （48RG）. The synaptic ultrastuncture was observed by transmission electron microscopy, the expression of PSD-95 protein was detected by immunohistochemistry and the correlation between ultrastructure and PSD-95 was analyzed. D2DR antagonist and agonist were used to interfere the autonomic exercise of rats with Open Field Test. Results： （ 1 ） The width of synaptic clefts of DLS decreased significantly in l FG compared with CG （P〈 0.01 ）, and the density of 3FG and 7FG decreased significantly （P〈 0.05 ） compared with CG and 1FG; （2） Compared with CA3 and 1FG, expression of PSD-95 protein in 24RG was significantly increased （P〈 0.05 ） （3） The total exercise distance of each group decreased gradually with the increase of exercise intensity, and the rest returned to a quiet level. Rats exhaustion time was significantly shortened after injection of D2DR antagonist （P〈 0.01 ）, while the agonist intervention significantly increased the exhaustion time （P〈 0.01 ）. Conclusions： PSD-95 has no correlation with the degree of exercise-induced fatigue, while exercise-induced fatigue reduced the ability of rats＇ autonomic activity. D2DR antagonist intervention made the exercise-induced fatigue condition deeply while D2DR agonist has convers role. The regulation of D2DR may be related to synaptic plasticity of dopaminergic microcirculation in the substantia nigra striatum, it suggests that D2DR can be selected as an important target for regulation exercise-induced fatigue.