Zou Yanghong, Huang Tao, Pang Ailan, Zhou Houjun, Geng Xin
The Second Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China; Yunnan Provincial Clinical Research Center for Neurological Disease, Kunming 650032, Yunnan, China.
Yunnan Provincial Clinical Research Center for Neurological Disease, Kunming 650032, Yunnan, China; Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.
Exp Gerontol. 2024 Oct 15;196:112558. doi: 10.1016/j.exger.2024.112558. Epub 2024 Aug 27.
Parkinson's disease (PD) is a common central neurodegenerative disease in middle-aged and elderly people. The progressive degeneration and death of dopaminergic neurons leads to insufficient dopamine (DA) neurotransmitters. Acupuncture and moxibustion can alleviate the aging of neurons. Therefore, studying the neuroprotective effects of electroacupuncture (EA) in PD mice is particularly important.
Intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was used to establish a PD mouse model, and lipopolysaccharide (LPS) was used to induce microglia polarization. Western blotting, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), Nissl staining and immunohistochemistry were used to detect neuronal apoptosis and injury, α-syn expression and microglial accumulation in PD mice. In addition, the levels of inflammatory factors were determined using enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the Ca content. The fluorescein isothiocyanate (FITC) labeling method was used to assess glucose uptake. A reagent kit was used to detect glucose and lactate levels.
MPTP induced the selective loss of DA neurons in the SN of mice, altered Ca homeostasis, and induced an inflammatory response. In addition, maintaining Ca homeostasis depends on the activity of transient receptor potential channel 1 (TRPC1). EA therapy promotes TRPC1 expression, which has a negative regulatory effect on sodium-glucose cotransporter 1 (SGLT1). Under the action of EA, TRPC1 protein expression increased, Ca concentrations increased, and the effect of SGLT1 was inhibited, thereby facilitating glucose metabolism, blocking the activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, restraining M1 polarization of microglia, and alleviating the PD process.
EA promotes TRPC1/Ca pathway activation, inhibits SGLT1-mediated regulation of glucose metabolism and PI3K/AKT pathway activation, inhibits microglial M1 polarization, and alleviates PD.
帕金森病（PD）是中老年人常见的中枢神经退行性疾病。多巴胺能神经元的进行性变性和死亡导致多巴胺（DA）神经递质不足。针灸可减轻神经元衰老。因此，研究电针（EA）对PD小鼠的神经保护作用尤为重要。
腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP，20mg/kg）建立PD小鼠模型，并用脂多糖（LPS）诱导小胶质细胞极化。采用蛋白质免疫印迹法、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）、尼氏染色和免疫组织化学法检测PD小鼠神经元凋亡与损伤、α-突触核蛋白表达及小胶质细胞聚集情况。此外，采用酶联免疫吸附测定（ELISA）法测定炎症因子水平。采用流式细胞术检测钙含量。采用异硫氰酸荧光素（FITC）标记法评估葡萄糖摄取。使用试剂盒检测葡萄糖和乳酸水平。
MPTP诱导小鼠黑质中DA神经元选择性丢失，改变钙稳态，并诱导炎症反应。此外，维持钙稳态依赖于瞬时受体电位通道1（TRPC1）的活性。EA治疗可促进TRPC1表达，其对钠-葡萄糖协同转运蛋白1（SGLT1）具有负调节作用。在EA作用下，TRPC1蛋白表达增加，钙浓度升高，SGLT1的作用受到抑制，从而促进葡萄糖代谢，阻断磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）通路的激活，抑制小胶质细胞M1极化，减轻PD进程。
EA促进TRPC1/钙通路激活，抑制SGLT1介导的葡萄糖代谢调节及PI3K/AKT通路激活，抑制小胶质细胞M1极化，减轻PD。
