运动干预通过减缓纹状体多巴胺丢失改善帕金森病模型大鼠行为功能的研究

Exercise Intervention Improving the Behavior function of the Rat Model of Parkinson's Disease by Slowing down the Loss of Dopamine in Striatum

目的:探讨跑台运动干预对帕金森病(Parkinson’s disease,PD)模型大鼠行为功能、纹状体多巴胺(dopamine,DA)含量的影响。方法:健康雄性SD大鼠,随机分为假手术安静组(Control组)、假手术运动组(Control+Ex组)、6-OHDA安静组(PD组)、6-OHDA运动组(PD+Ex组)。依据实验设计要求,PD和PD+Ex组右脑内侧前脑束(MFB)注射6-羟基多巴胺(6-OHDA)建立偏侧PD大鼠模型,假手术组于相同位点注射等量生理盐水。在造模后的第7天颈部皮下注射阿朴吗啡(APO)进行旋转行为测试,评价PD模型的可靠性,不符合PD模型标准的大鼠剔除。运动组术后1周开始进行跑台训练,运动方案为11 m/min,30 min/day,5 days/week,共4周。采用旷场试验评价PD模型大鼠的自主活动能力;微透析-高效液相色谱电化学联用技术检测纹状体DA浓度;免疫组织化学检测纹状体酪氨酸羟化酶(TH)阳性纤维的表达。结果:PD和PD+Ex组移动距离较Control组显著降低(P<0.01);PD+Ex组第3、4周移动距离较PD组显著增加(P<0.01)。PD和PD+Ex组纹状体DA含量较Control组显著降低(P<0.01);但PD+Ex组第3、4周纹状体DA浓度较PD组显著升高(P<0.01)。结论:PD模型大鼠总移动距离与纹状体DA浓度之间存在高度正相关,且二者均随6-OHDA药物及运动干预持续时间延长出现"时序性"变化特征。运动干预通过减缓纹状体DA丢失改善PD模型大鼠自主行为功能,推测其机制可能与运动的神经保护作用减轻了6-OHDA神经毒素对DA能神经元的毒性损伤、促进其存活有关。

Objective To explore the effect of the treadmill exercise intervention on the behaviorfunction and the concentration of dopamine in the striatum of the rat model of Parkinson＇s disease（PD）. Methods Healthy male Sprague-Dawley rats were randomly divided into a sham operation quiet（Control） group,sham-operation＋Exercise（Control ＋ Ex） group,6-hydroxydopamine（6-OHDA） quiet（PD） group,and 6-OHDA＋Exercise（PD ＋ Ex） group. PD and PD ＋ Ex groups were injected 6-OH-DA into the right medial forebrain bundle to establish the unilateral PD rat model,while the sham oper-ation groups were injected the same amount of physiological saline at the same site. On the 7 th days after modeling,the rats were subcutaneously injected Apo morphine for rotational behavior test to ex-clude those not meeting the requirements for the PD model. One week after the operation,the exercisegroup started treadmill training at the speed of 11 m/min,30 min/day and 5 days/week,for a total offour weeks. The locomotor activity of PD rats was evaluated using the open field test. The DA concen-tration in striatum was detected using micro dialysis high performance liquid chromatography and elec-trochemistry. The expression of tyrosine hydroxylase positive fiber in the striatum was assessed usingthe immunohistochemistry. Results Compared with the Control group,significant decrease was observedin the moving distance of PD and PD ＋ Ex groups（P〈0.01）,while significant increase was found ofPD ＋ Ex group compared with PD group after 3 and 4 weeks of training（P〈0.01）. Compared with theControl group,DA concentration in the striatal decreased significantly in PD and PD ＋ Ex groups,butthat of PD ＋ Ex group increased significantly after 3 and 4 weeks＇ training compared with the PDgroup（P〈0.01）. Conclusion There is a highly positive correlation between the total moving distanceand the DA concentration in the striatum of PD rats. The moving distance and the DA concentrationboth have changed ＂sequentially＂ with the prolongation of 6-OHDA and exercise intervention. The exer-cise intervention can reduce the DA loss of the striatum and improve the locomotor function of PDrats. It is presumed that the mechanism may be related to the neuroprotective effect of exercise,whichcan reduce the damage of 6-OHDA neurotoxin to DA neurons and promote their survival.