运动通过调节纹状体A2AR/D2DR表达改善帕金森病模型大鼠行为功能障碍  

Exercise Regulates Striatum A2AR/D2DR Expression to Improve Behavioral Dysfunction of PD Rats

作　　者：刘晓莉[1] 赵刚 王弘[1] 王宗兵[1] 张丹昱 Liu Xiaoli;Zhao Gang;Wang Hong;Wang Zongbing;Zhang Danyu(College of Physical Education and Sports of Beijing Normal university,Beijing 100875,China)

机构地区：[1]北京师范大学体育与运动学院,北京100875

出　　处：《中国运动医学杂志》2020年第5期381-389,共9页Chinese Journal of Sports Medicine

基　　金：国家自然科学基金项目(31571221)。

摘　　要：目的:揭示纹状体腺苷2A型受体(A2AR)、多巴胺Ⅱ型受体(D2DR)在运动干预改善帕金森病(PD)模型大鼠行为功能障碍中的作用。方法:选用雄性SD大鼠,随机分为假手术组(Control组,n=22)、假手术运动组(Control+Ex组,n=22)、帕金森组(PD组,n=38)和帕金森运动组(PD+Ex组,n=38)。注射6-羟基多巴胺(6-OHDA)建立偏侧PD大鼠模型,术后24 h对运动组大鼠进行4周跑台运动干预(11 m/min,30 min/day,5 days/week),通过阿扑吗啡(APO)诱导旋转行为和黑质酪氨酸羟化酶(TH)表达鉴定PD大鼠模型可靠性。采用荧光定量PCR和免疫荧光技术检测纹状体A2AR和D2DR基因转录和蛋白表达;通过A2AR拮抗剂SCH联合D2DR激动剂QUIN干预进一步证实PD大鼠行为功能改善与纹状体A2AR-D2DR表达之间的相关性。结果:注射6-OHDA大鼠健侧旋转圈数与损毁侧旋转圈数差值>100 r/30 min,黑质TH表达较Control组降低(P<0.001),符合PD大鼠模型标准。4周跑台运动干预后,PD大鼠A2AR及D2DR基因转录及蛋白表达逆转,且与PD组相比有显著差异(P<0.01,P<0.05)。4周跑台运动干预可显著减少SCH和QUIN药物诱导PD大鼠旋转圈数增加的现象(P<0.05)。注射SCH和QUIN后PD大鼠向健侧旋转圈数与A2AR-D2DR阳性细胞数成正相关(r=0.815,P<0.01)。结论:早期运动干预减轻了6-OHDA药物对大鼠黑质多巴胺(DA)能神经元的毒性损伤,调节纹状体A2AR及D2DR基因转录及蛋白表达,改善了PD模型大鼠行为障碍。本研究结果初步证实,纹状体A2AR、D2DR是运动纠正PD模型大鼠基底神经节直接与间接通路失衡的重要细胞分子靶点。推测其机制可能与运动的神经保护作用改善了PD大鼠黑质-纹状体DA能通路的突触可塑性有关。Objective To reveal the role of striatum adenosine 2 A receptor(A2 AR)and dopamine type 2 receptor(D2 DR)in the exercise intervention to improve behavioral dysfunction of rats with Parkinson’s disease(PD).Methods Totally 120 male Sprague-Dawley rats were selected and randomly divided into a sham-operation group(Control,n=22),and a sham-operation group doing exercise(Control+Ex,n=22),a PD group(PD,n=38)and a Parkinson’s disease group doing exercise(PD+Ex,n=38).The unilateral PD was induced in rats by injecting 6-Hydroxydopamine(6-OHDA)and the rats in the exercise groups were subjected to a 4-week treadmill exercise intervention(11 m/min,30 min/day,5 days/week)24 h after the operation.The reliability of PD rat model was confirmed using the APO-induced rotational behavior and tyroxine hydroxylase(TH)expression in the substantia-nigra pars compacta.The mRNA and protein expressions of A2 AR and D2 DR in the striatum were detected using the real-time PCR and immunofluorescence.The correlation between behavioral function improvement and striatum A2 AR-D2 DR protein expression of PD rats was evaluated using the A2 AR antagonist SCH combined with D2 DR agonist QUIN.Results The gap in the number of rotations between the healthy and lesion side of 6-OHDA rats was>100 r/30 min,and the expression of TH in the substantia nigra was significantly lower than that of the Control group(P<0.001),which met the standards of the PD rat model.After a 4-week treadmill exercise,the gene transcription and protein expression of A2 AR and D2 DR of PD rats were reversed,showing significant differences compared with PD group(P<0.01,P<0.05).The 4-weeks treadmill exercise intervention could significantly reduce the number of rotations induced by SCH and QUIN(P<0.05).Moreover,the number of rotations to the contralateral side after the injection of SCH and QUIN was positively correlated with the number of A2 AR-D2 DR positive cells(r=0.815,P<0.01).Conclusion Early exercise intervention can alleviate the toxic damage of 6-OHDA on rat substantia

关 键 词：运动干预 帕金森病 纹状体 腺苷2A型受体、多巴胺Ⅱ型受体 行为功能障碍 

分 类 号：R87[医药卫生—运动医学] R742.5[医药卫生—临床医学]