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跑台运动通过激活自噬改善慢性帕金森病小鼠便秘

聂碧徽^1,2, 高原^1,3, 刘小倩^1,2, 刘德坤^1,2, 寇现娟^1,2,*

¹武汉体育学院运动医学院，武汉 430079；²运动训练监控湖北省重点实验室，武汉 430079；³哈尔滨体育学院，哈尔滨 150008

摘要

本文旨在探究8周跑台运动对慢性帕金森病(Parkinson's disease, PD)小鼠便秘症状的影响及其分子机制。将40只C57BL/6 小鼠随机分为4 组：对照(Control)组、模型(PD)组、8 周跑台运动(PD+Ex)组、8 周跑台运动+3-甲基腺嘌呤(3-methyladenine, 3MA) (PD+Ex+3MA) 组， 每组n = 10。用1- 甲基-4- 苯基-1, 2, 3, 6- 四氢吡啶(1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, MPTP)联合丙磺舒(probenecid) (MPTP/p)制备慢性PD 小鼠模型，PD+Ex 组进行8 周跑台运动训练，PD+Ex+3MA组额外接受5 周3MA腹腔注射(与造模同时进行)。用排便参数、结肠长度和肠比重等指标评估便秘症状，用免疫荧光染色法检测结肠α-突触核蛋白(α-synuclein, α-syn)沉积，用RT-qPCR 检测结肠神经递质关键酶mRNA 表达水平，用Western blot 检测病理蛋白和自噬相关蛋白表达。结果显示，与Control 组相比，PD组小鼠出现运动功能障碍和明显便秘症状，纹状体酪氨酸羟化酶(tyrosine hydroxylase, TH)蛋白表达显著下调，结肠中α-syn沉积明显且蛋白表达显著上调，神经元型一氧化氮合酶(neuronal nitric oxide synthase, nNOS) mRNA表达上调，TH蛋白和胆碱乙酰转移酶(choline acetyltransferase,ChAT) mRNA表达下调，p62 蛋白表达上调，Beclin1 和LC3Ⅱ蛋白表达下调；跑台运动干预后PD组小鼠以上变化均得到显著改善，而自噬抑制剂3MA可抵消跑台运动干预的这些改善作用。上述结果提示，8 周跑台运动能够改善MPTP/p诱导的慢性PD小鼠便秘症状，其保护作用可能是通过激活自噬来实现的。

关键词： 帕金森病; 便秘; 自噬; 跑台运动

Treadmill exercise improves constipation in mice with chronic Parkinson's disease through activating autophagy

NIE Bi-Hui^1,2, GAO Yuan^1,3, LIU Xiao-Qian^1,2, LIU De-Kun^1,2, KOU Xian-Juan^1,2,*

¹College of Sports Medicine, Wuhan Sports University, Wuhan 430079, China；²Hubei Key Laboratory of Exercise Training and Monitoring, Wuhan 430079, China；³Harbin Sports University, Harbin 150008, China

Abstract

This study aimed to explore the effects and molecular mechanisms of 8-week treadmill exercise on constipation symptoms in mice with chronic Parkinson's disease (PD). Forty C57BL/6 mice were randomly divided into four groups: control group, model (PD) group, 8-week treadmill exercise (PD+Ex) group, and 8-week treadmill exercise+3-methyladenine (3MA) (PD+Ex+3MA) group, with n = 10 in each group. A chronic PD mouse model was prepared using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) combined with probenecid (MPTP/p). The PD+Ex group underwent 8 weeks of treadmill exercise training, while the PD+Ex+3MA group received an additional 5 weeks of 3MA intraperitoneal injection (simultaneously with modeling). Constipation symptoms were evaluated using indicators such as defecation parameters, colon length, and colon to body weight ratio. Immunofluorescence staining was used to detect α-synuclein (α-syn) deposition in the colon. RT-qPCR was used to detect the mRNA expression levels of key enzymes of neurotransmitters in the colon, and Western blot was used to detect pathological and autophagy-related protein expression levels. The results showed that, compared with the control group, the PD group mice exhibited motor dysfunction and significant constipation symptoms. In the PD group, the protein expression of tyrosine hydroxylase (TH) in the striatum was significantly downregulated, while α-syn deposition in the colon was significant and its protein expression was significantly up-regulated. The mRNA expression of neuronal nitric oxide synthase (nNOS) was up-regulated, while the expression levels of TH protein and choline acetyltransferase (ChAT) mRNA were down-regulated in the colon. The protein expression of p62 was up-regulated, and the protein expression levels of Beclin1 and LC3II were down-regulated in the colon. After treadmill exercise intervention, all the above changes in the PD group were significantly improved, and autophagy inhibitor 3MA could counteract these improving effects of treadmill exercise intervention. These results suggest that 8-week treadmill exercise can improve constipation symptoms in MPTP/p-induced chronic PD mice, and its protective effect may be achieved by activating autophagy.

Key words: Parkinson''s disease; constipation; autophagy; treadmill exercise

收稿日期：　　录用日期：

通讯作者：寇现娟　　E-mail:

DOI: 10.13294/j.aps.2025.0091

引用本文：

聂碧徽, 高原, 刘小倩, 刘德坤, 寇现娟. 跑台运动通过激活自噬改善慢性帕金森病小鼠便秘[J]. 生理学报 2025; 77 (6): 1187-1200.

NIE Bi-Hui, GAO Yuan, LIU Xiao-Qian, LIU De-Kun, KOU Xian-Juan. Treadmill exercise improves constipation in mice with chronic Parkinson's disease through activating autophagy. Acta Physiol Sin 2025; 77 (6): 1187-1200 (in Chinese with English abstract).