Objective To explore the effect of electroacupuncture participating in the behavioral response and brain autophagy of Parkinson's rats by regulating phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR). Methods Sixty rats were randomly separated into a control group, a Parkinson's group, an electroacupuncture group, a sirolimus group, an electroacupuncture + PI3K activation group, with 12 rats in each group. The Parkinson's rat model was prepared, and the motor behavioral function of the rats was evaluated by the inclined plate test and the open field test. The expression of tyrosine hydroxylase (TH) and α-synuclein (α-syn) in substantia nigra was measured by immunohistochemistry. Brain tissue mitochondria were extracted, ATP synthase activity was measured by luciferase labeling method, and mitochondrial activity was measured by mitochondrial respiration detector. The expression levels of PI3K, AKT, mTOR, p-PI3K, p-AKT, p-mTOR and autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3) B-II/LC3B-I, and Beclin1 in brain tissue were measured by Western blot. Results Compared with the control group, the Parkinson's group showed a significant decrease in the maximum angle of sloping plate stay, times of crossings lattice, times of standing, RCR in brain tissue, ATP synthase activity, and the average optical density of TH in the substantia nigra, and a significant increase in α-syn, Beclin1 protein expression, LC3B-II/LC3B-I and PI3K, AKT, mTOR protein phosphorylation (P<0.05). Compared with the Parkinson's group, the EA group and the sirolimus group showed significant increase in the maximum angle of sloping plate stay, times of crossings lattice, times of standing, RCR in brain tissue, ATP synthase activity, Beclin1 protein expression, LC3B-II/LC3B -I, and average optical density of TH in the substantia nigra, and significant decrease in the expression of α-syn protein and the protein phosphorylation of PI3K, AKT and mTOR (P<0.05). Compared with the electroacupuncture group, the rats in the electroacupuncture + PI3K activation group had a significant decrease in the maximum angle of sloping plate stay, times of crossings lattice, times of standing, RCR in brain tissue, ATP synthase activity, Beclin1 protein expression, LC3B-II/LC3B -I, and average optical density of TH in the substantia nigra, and a significant increase in the expression of α-syn protein and the protein phosphorylation of PI3K, AKT and mTOR (P<0.05). Compared with the electroacupuncture group, there was no significant difference in the indicators in the sirolimus group (P>0.05). Conclusions Electroacupuncture can inhibit the phosphorylation of PI3K, AKT and mTOR proteins, activate autophagy, and improve the motor behavioral function of rats, so as to treat the clinical symptoms of Parkinson's disease.
Key words
Parkinson's disease /
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Electroacupuncture /
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Phosphatidylinositol 3-kinase /
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Protein kinase B /
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Mammalian target of rapamycin
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References
[1] Kilpatrick MM, Robinson MT. Addressing spiritual well-being as a means of improving quality of life in Parkinson disease[J]. Ann Palliat Med, 2020, 9(2): 133-135. DOI: 10.21037/apm.2019.11.30.
[2] Deuschl G, Schade-Brittinger C, Krack P, et al. A randomized trial of deep-brain stimulation for Parkinson's disease[J]. N Engl J Med, 2006, 355(9): 896-908. DOI: 10.1056/NEJMoa060281.
[3] Zhu J, Dou S, Jiang Y, et al. Apelin-36 exerts the cytoprotective effect against MPP+-induced cytotoxicity in SH-SY5Y cells through PI3K/Akt/mTOR autophagy pathway[J]. Life Sci, 2019, 224(1): 95-108. DOI: 10.1016/j.lfs.2019.03.047.
[4] Chu F, Li K, Li X, et al. Graphene oxide ameliorates the cognitive impairment through inhibiting PI3K/Akt/mTOR pathway to induce autophagy in AD mouse model[J]. Neurochem Res, 2021, 46(2): 309-325. DOI: 10.1007/s11064-020-03167-z.
[5] Chen Y, Zheng X, Wang Y, et al. Effect of PI3K/Akt/mTOR signaling pathway on JNK3 in Parkinsonian rats[J]. Exp Ther Med, 2018, 17(3): 1771-1775. DOI: 10.3892/etm.2018.7120.
[6] Alexandra D, Dharmakaya CD, Barry O. Local and systemic analgesic effects of nerve-specific acupuncture in healthy adults, measured by quantitative sensory testing[J]. Pain Med, 2020, 21(2): 232-242. DOI: 10.1093/pm/pnz276.
[7] Tang HY, Wang FJ, Ma JL, et al. Acupuncture attenuates the development of diabetic peripheral neuralgia by regulating P2X4 expression and inflammation in rat spinal microglia[J]. J Physiol Sci, 2020, 70(1): 45-48. DOI: 10.1186/s12576-020-00769-8.
[8] Hsu WT, Chen YH, Yang HB, et al. Electroacupuncture improves motor symptoms of parkinson's disease and promotes neuronal autophagy activity in mouse brain[J]. Am J Chin Med, 2020, 48(7): 1651-1669. DOI: 10.1142/S0192415X20500822.
[9] 李亚楠, 马骏, 余沛豪, 等. 鱼藤酮帕金森病模型的建立与评价[J]. 中华中医药学刊, 2020, 38(3): 175-179. DOI: 10.13193/j.issn.1673-7717.2020.03.046.
[10]张如意, 张丽, 吴燕川, 等. 不同剂量鱼藤酮对拟帕金森病模型大鼠行为学及纹状体多巴胺含量的影响[J]. 中国比较医学杂志, 2013, 23(9): 1-5. DOI: 10.3969.j.issn.1671.7856.2013.009.001.
[11]Dayan E, Sklerov M. Autonomic disorders in parkinson disease: disrupted hypothalamic connectivity as revealed from resting-state functional magnetic resonance imaging[J]. Handb Clin Neurol, 2021, 182(1): 211-222. DOI: 10.1016/B978-0-12-819973-2.00014-9.
[12]吕妙君, 冯鹏, 郭雅静, 等. 新型肠促胰岛素双受体激动剂对亚急性帕金森病小鼠步态行为的影响及机制研究[J]. 中华老年心脑血管病杂志,2021,23(9): 908-912. DOI: 10.3969/j.issn.1009-0126. 2021. 09. 004.
[13]Patel M, Urits I, Kaye AD, et al. The role of acupuncture in the treatment of chronic pain[J]. Best Pract Res Clin Anaesthesiol, 2020, 34(3): 603-616. DOI: 10.1016/j.bpa.2020.08.005.
[14]王静, 王安龙, 范小明, 等. 经颅超声对电针治疗帕金森病模型大鼠的效果评价[J]. 中华医学超声杂志:电子版, 2020, 17(1): 70-75. DOI: 10.3877/cma.j.issn.1672-6448.2020.01.013.
[15]李昆珊, 徐世芬, 李璟, 等. 电针配合药物治疗帕金森病的临床研究[J]. 上海针灸杂志, 2020, 39(12): 1564-1569. DOI: 10.13460/j.issn.1005-0957.2020.13.1038.
[16]朱锋, 范苗, 徐孜惟, 等. 雷帕霉素对帕金森病小鼠的保护作用[J]. 浙江大学学报:医学版, 2018, 47(5): 465-472. DOI: 10.3785/j.issn.1008-9292.2018.10.04.
[17]孙江萌, 沈丽华, 杨颖, 等. 血清α-突触核蛋白及UCH-L1水平与帕金森病的相关性研究[J]. 南通大学学报:医学版, 2020, 40(4): 318-321. DOI: 10.16424/j.cnki.cn32-1807/r.2020.04.006.
[18]钟娟, 陈静, 青姚, 等. 川芎嗪通过抑制PI3K/Akt/mTOR通路诱导自噬改善糖尿病肾病大鼠肾损害[J]. 天津医药, 2019, 47(4): 395-400. DOI: 10.11958/20181506.
[19]吴忧, 梁顺利, 徐彬, 等. 姜黄素通过抑制PI3K/Akt/mTOR通路增强自噬保护帕金森病细胞模型的研究[J]. 中国现代应用药学, 2021, 38(19): 2351-2358. DOI: 10.13748/j.cnki.issn1007-7693.2021.19.003.
[20]高睿琦. 电针对失神经性骨骼肌萎缩大鼠PI3K/Akt/mTOR信号通路相关蛋白的影响[D]. 重庆: 重庆医科大学, 2017. DOI: 10.7666/d.D01261039.
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