Abstract
Objective
To observe the effects of acupuncture on the motor function of Parkinson disease (PD) model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.
Methods
C57BL/6J mice were randomly divided into a normal control (NC) group, a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) group, an acupuncture (ACU) group, and a rasagiline (RAS) group, with 6 mice in each group. Except for the mice in the NC group, all mice were injected intraperitoneally with MPTP [30 mg/(kg·bw)] to establish a PD mouse model. After the models were successfully established, mice in the ACU group received acupuncture at Baihui (GV20) and bilateral Yanglingquan (GB34) for 15 min, once a day for 14 consecutive days. Mice in the RAS group were treated with gavage of rasagiline mesylate [0.5 mg/(kg·bw)], once daily for 14 d. Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus. Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase (TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1 (SATB1), p21, and p53 in the substantia nigra (SN) region of the mouse brain in each group. The glutathione peroxidase (GSH-Px) activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay. The protein expression levels of interleukin (IL)-6 and senescence-associated β-galactosidase (SA-β-gal) in the SN tissue of mice in each group were detected by Western blotting. The relative expression of SATB1, p21, and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.
Results
Compared with the NC group, the overall rod performance (ORP) score, the number of TH-positive neurons, and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group (P<0.01); compared with the MPTP group, the ORP score, the number of TH-positive neurons, and GSH-Px activity were significantly increased in the ACU and RAS groups (P<0.01 or P<0.05). Compared with the NC group, the protein levels of IL-6 and SA-β-gal in the SN tissue, the protein and mRNA expression levels of p21 and p53 were significantly increased (P<0.01); compared with the MPTP group, the protein levels of IL-6 and SA-β-gal in the SN tissue, the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group (P<0.01 or P<0.05). Compared with the NC group, the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased (P<0.01); compared with mice in the MPTP group, mice in the ACU and RAS groups showed significant increases in the relative expression of SATB1 protein and mRNA (P<0.01 or P<0.05).
Conclusion
Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice. Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.
摘要
目的
观察针刺对帕金森病(PD)模型小鼠运动功能的影响, 并从细胞衰老角度探究针刺对PD的神经保护 作用。
方法
将C57BL/6J小鼠随机分为正常(NC)组、1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)组、针刺(ACU)组和雷 沙吉兰(RAS)组, 每组6只。除正常组小鼠外, 其余各组小鼠腹腔注射MPTP[30 mg/(kg·bw)]构建PD小鼠模型。ACU 组小鼠予针刺百会和双侧阳陵泉, 每次15 min, 每日1次, 连续治疗14 d。雷沙吉兰组小鼠采用甲磺酸雷沙吉兰 [0.5 mg/(kg·bw)]进行灌胃治疗, 每日1次, 连续治疗14 d。采用疲劳转棒仪检测小鼠平衡和运动能力。采用免疫 组织化学染色法检测各组小鼠脑黑质部位TH阳性神经元数量和SATB1、p21、p53蛋白表达水平。采用酶联免疫 吸附法检测小鼠中脑黑质组织谷胱甘肽过氧化物酶(GSH-Px)活力。采用免疫印迹法检测各组小鼠脑黑质组织白 细胞介素(IL)-6、衰老相关β-半乳糖苷酶(SA-β-gal)蛋白表达水平。采用实时荧光定量逆转录聚合酶链式反应检 测各组小鼠中脑黑质组织AT富集序列特异性结合蛋白1(SATB1)、p21、p53 mRNA相对表达量。
结果
与NC组相 比, MPTP组小鼠转棒实验(ORP)评分、中脑黑质区域TH阳性神经元数量和GSH-Px活性显著降低(P<0.01); 与MPTP 组相比, ACU组和RAS组ORP评分、TH阳性神经元数量和GSH-Px活性显著增加(P<0.01或P<0.05)。与NC组相比, MPTP组小鼠中脑黑质IL-6和SA-β-gal蛋白、p21与p53的蛋白及mRNA表达水平显著增加(P<0.01); 与MPTP组相比, ACU组和RAS组小鼠中脑黑质IL-6和SA-β-gal蛋白、p21与p53的蛋白及mRNA表达水平显著降低(P<0.01或 P<0.05)。与NC组相比, MPTP组小鼠中脑黑质SATB1蛋白和mRNA相对表达量显著降低(P<0.01); 与MPTP组小鼠相 比, ACU组和RAS组小鼠SATB1蛋白和mRNA相对表达量显著增加(P<0.01或P<0.05)。
结论
针刺可以改善PD模型小 鼠运动功能, 增加黑质部位TH阳性神经元数量。针刺对PD小鼠的神经保护作用可能与调节SATB1/p21信号通路, 抑制黑质细胞衰老相关生物标志物表达有关。
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Acknowledgments
This work was supported by High Level Traditional Chinese Medicine Key Subjects of the State Administration of Traditional Chinese Medicine (国家中 医药管理局高水平中医药重点学科建设项目, No. zyyzdxk-2023068); Project of National Natural Science Foundation of China (国家自然科学基金项目, No. 82205260); Shanghai Pudong New Area Health System Famous Traditional Chinese Medicine Training Program (上海市浦东新区卫计委名中医培养计划, No. PWRzm2020-12); Discipline Construction of Pudong New Area Health Commission Acupuncture and Moxibustion Key Specialty of Traditional Chinese Medicine (浦东新区 卫计委学科建设中医针灸重点专科, No. PWZzk2022-25).
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Statement of Human and Animal Rights
This experiment passed the ethical review of experimental animals in Yueyang Hospital of Integrative Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (Ethical Approval No. YYLAC-2020-070-1). The treatment of animals in this experiment conformed to the ethical criteria.
Co-first Authors: LI Guona, M.M., physician; WANG Zhaoqin, M.D., associate professor
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Li, G., Zhao, C., Wang, Z. et al. Effects of acupuncture on SATB1/p21 signaling pathway and SASPs in MPTP-induced Parkinson disease model mice. J. Acupunct. Tuina. Sci. (2024). https://doi.org/10.1007/s11726-024-1426-4
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DOI: https://doi.org/10.1007/s11726-024-1426-4
Keywords
- Acupuncture Therapy
- Point, Baihui (GV20)
- Point, Yanglingquan (GB34)
- Parkinson Disease
- Signal Transduction
- Cell Aging
- Mice