技巧性有氧训练对PD大鼠运动行为和中脑内质网应激的影响

Effects of skilled aerobic exercise on motor behavior and endoplasmic reticulum stress in rats with Parkinson’s disease

目的观察技巧性有氧训练(skilled aerobic exercise,SAE)对帕金森病(Parkinson’s disease,PD)大鼠运动功能、中脑内质网应激(endoplasmic reticulum stress,ERS)、血清Irisin含量、酪氨酸羟化酶(TH)和大鼠骨骼肌FNDC5表达的影响。方法将60只SD大鼠随机分为假手术组、模型组、假手术+技巧运动组和模型+技巧运动组,每组15只。其中30只大鼠采用单侧两点注射法定向注射6羟基多巴胺建立PD模型和30只大鼠注射生理盐水建立假手术组模型。将造模后的15只PD大鼠和15只假手术大鼠进行连续28 d技巧性有氧训练,其余大鼠进行28 d随意运动。分别于运动7,14,28 d采用阿扑吗啡(apomorphine,Apo)诱导大鼠的旋转行为、圆柱体试验观察大鼠前肢的运动功能。运动28 d分别采集各组大鼠中脑组织、大鼠左后肢股四头肌组织和腹主动脉血样本,采用免疫组织化学检测中脑酪氨酸羟化酶(tyrosine hydroxylase,TH)的表达,Western blot法检测中脑组织Bip/Grp78、CHOP和骨骼肌FNDC5的表达,ELISA法检测血清Irisin水平。结果与假手术组比较,模型组大鼠中脑TH和骨骼肌FNDC5表达明显下调,血清Irisin含量下降,中脑组织内质网应激水平增加,前肢运动能力下降,Apo诱导的旋转行为明显增加,差异均有统计学意义(P<0.05)。与模型组比较,经14 d技巧性有氧训练,模型+技巧运动组大鼠的旋转行为明显减少(P<0.05);经28 d技巧性有氧训练,模型+技巧运动组大鼠的前肢运动能力明显增强,中脑TH和骨骼肌FNDC5表达增加,血清Irisin含量升高,内质网应激水平下降,差异均有统计学意义(P<0.05)。结论中长期的技巧性有氧训练可以上调大鼠骨骼肌FNDC5的表达,升高血清Irisin含量,降低中脑的内质网应激水平、减缓中脑黑质DA神经元的丢失,改善PD模型大鼠的运动能力。

Objective To observe the effects of skilled aerobic exercise(SAE)on motor function,endoplasmic reticulum stress(ERS),serum content of Irisin,expression of tyrosine hydroxylase(TH)in midbrain and FNDC5 in skeletal muscle of rats with Parkinson’s disease(PD).Methods Sixty SD rats were randomly divided into sham operation group,model group,sham operation+SAE group and model+SAE group,with 15 rats in each group.The PD models were established by unilateral two-point injection of 6-hydroxydopamine in 30 rats and the sham operation models were injected with normal saline in 30 rats.After modeling,15 PD rats and 15 sham rats underwent SAE for 28 d,and the rest rats underwent random exercise for 28 d.Apomorphine(Apo)was used to induce the rotation behavior,and cylindrical test was used to observe the forelimb motor function of rats at 7,14,28 d after exercise.After 28 d exercise,midbrain tissue,quadriceps femoris muscle tissue and blood samples in abdominal aorta of rats in each group were collected.The expression of TH in midbrain was detected by immunohistochemistry,the expression of Bip/Grp78,CHOP in midbrain and FNDC5 in muscle tissues was detected by Western blot,and the level of Irisin in serum was detected by ELISA.Results Compared with sham operation group,the expression of TH in midbrain and FNDC5 in skeletal muscle was significantly down-regulated in model group,the content of Irisin in serum was decreased,the level of ERS in midbrain tissues was increased,the movement ability of forelimbs was decreased,and the rotation behavior induced by Apo was significantly increased(all P<0.05).Compared with model group,the rotation behavior of rats was significantly reduced after 14 d of SAE in model+SAE group(P<0.05).After 28 d of SAE,compared with model group,the forelimb motor ability in model+SAE group was significantly enhanced,the expression of TH in midbrain and FNDC5 in skeletal muscle was increased,the content of Irisin in serum was increased,and the level of ERS was decreased(all P<0.05).Conclusion Mid-long term SAE could up-regulate the expression of FNDC5 in skeletal muscle,increase the content of Irisin in serum,reduce the level of ERS in midbrain,reduce the loss of DA neurons in midbrain,and improve the motor function of PD model rats.