Modulating the WNK1-SPAK/OSR1-KCC2 Pathway: Acupuncture’s Therapeutic Potential in Mitigating Muscle Hypertonia in Ischemic Stroke Rats

IF 4.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemical Research Pub Date : 2026-10-20 DOI:10.1007/s11064-026-04927-z

Tian-Yi Sun, Liang-Xiao Ma, Wen-Xu Zhang, Si-Biao Lu, Jing-Yun Xiu, Meng-Yu Chen

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Abstract

This study investigated the therapeutic effects of acupuncture on post-stroke muscle hypertonia (PSMH) in rats, focusing on the WNK1-SPAK/OSR1-KCC2 pathway to elucidate its underlying mechanisms and support clinical translation. Behavioral, electrophysiological, TTC staining, AChE staining, and transmission electron microscope analyses were used to assess the efficacy of acupuncture. RT-qPCR, Western blot, and immunofluorescence were used to evaluate the expression of the medullary WNK1-SPAK/OSR1-KCC2 pathway. Pharmacological modulation using WNK463 and Gabazine suggested the involvement of WNK kinase activity. Acupuncture reduced neurological deficits and spasticity, enhanced motor recovery, suppressed spinal motor neuron hyperexcitability, and ameliorated neuromuscular dysfunction and muscular structural abnormality. Mechanistically, it downregulated WNK1, SPAK, and OSR1 and increased membrane KCC2 expression in the medulla oblongata. WNK463 partially mimicked acupuncture’s effects, while Gabazine partially reversed them. Acupuncture alleviates muscle hypertonia and enhances locomotor recovery in rats with PSMH, potentially by inhibiting the medullary WNK1-SPAK/OSR1 pathway and thereby upregulating KCC2 expression and membrane localization.

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调节WNK1-SPAK/OSR1-KCC2通路：针刺减轻缺血性脑卒中大鼠肌肉高张力的治疗潜力

本研究探讨针刺对大鼠脑卒中后肌肉高张力（PSMH）的治疗作用，重点研究WNK1-SPAK/OSR1-KCC2通路，以阐明其潜在机制并支持临床翻译。采用行为学、电生理、TTC染色、AChE染色、透射电镜等方法评价针刺的疗效。采用RT-qPCR、Western blot和免疫荧光法检测髓质WNK1-SPAK/OSR1-KCC2通路的表达。使用WNK463和Gabazine的药理学调节提示WNK激酶活性的参与。针刺可减少神经功能缺损和痉挛，增强运动恢复，抑制脊髓运动神经元的过度兴奋性，改善神经肌肉功能障碍和肌肉结构异常。在机制上，它下调了WNK1、SPAK和OSR1，并增加了延髓中膜KCC2的表达。WNK463部分模仿了针灸的效果，而Gabazine部分逆转了针灸的效果。针刺可能通过抑制髓质WNK1-SPAK/OSR1通路，从而上调KCC2表达和膜定位，从而缓解PSMH大鼠的肌肉高张力并增强运动恢复。

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来源期刊

Neurochemical Research 医学-神经科学

CiteScore

7.70

自引率

2.30%

发文量

320

审稿时长

6 months

期刊介绍： Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.