Effect of Tuina at "Weizhong （BL 40）" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury

ZHANG Tianwei; LYU Xiangqian; XING Yani; ZHU Liuchen; ZHU Qingguang; KONG Lingjun; CHENG Yanbin; YAN Zhen; SUN Wuquan; FANG Min; WU Zhiwei

doi:10.13288/j.11-2166/r.2025.07.013

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Effect of Tuina at "Weizhong （BL 40）" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury

更新时间：2025-03-27

- Effect of Tuina at "Weizhong （BL 40）" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury
  增强出版
- Journal of Traditional Chinese Medicine Vol. 66, Issue 7, Pages: 734-740(2025)
- 作者机构：
  
  1.上海中医药大学附属岳阳中西医结合医院，上海市虹口区甘河路110号，200437
  2.上海中医药大学针灸推拿学院
  3.上海中医药大学中药学院
  4.上海市中医药研究院中医推拿研究所
  5.上海中医药大学附属曙光医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.07.013
  CLC：
- Received：17 December 2024，
  
  Revised：2025-02-03，
  
  Published：02 April 2025
- 稿件说明：
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张天伟,吕向前,邢雅妮等.推拿“委中”穴对坐骨神经慢性压迫损伤模型大鼠脊髓小胶质细胞活化相关蛋白及IL-10/β-EP通路的影响[J].中医杂志,2025,66(07):734-740.

ZHANG Tianwei,LYU Xiangqian,XING Yani,et al.Effect of Tuina at "Weizhong （BL 40）" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury[J].Journal of Traditional Chinese Medicine,2025,66(07):734-740.
张天伟,吕向前,邢雅妮等.推拿“委中”穴对坐骨神经慢性压迫损伤模型大鼠脊髓小胶质细胞活化相关蛋白及IL-10/β-EP通路的影响[J].中医杂志,2025,66(07):734-740. DOI： 10.13288/j.11-2166/r.2025.07.013.

ZHANG Tianwei,LYU Xiangqian,XING Yani,et al.Effect of Tuina at "Weizhong （BL 40）" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury[J].Journal of Traditional Chinese Medicine,2025,66(07):734-740. DOI： 10.13288/j.11-2166/r.2025.07.013.

摘要

目的

探讨推拿“委中”穴对坐骨神经慢性压迫损伤（CCI）模型大鼠神经病理性疼痛的缓解作用及可能的脊髓中枢机制。

方法

32只SD大鼠随机分为假手术组、模型组、推拿组和阻断组，每组8只。模型组、推拿组和阻断组均采用羊肠线坐骨神经结扎制备CCI模型，假手术组仅暴露坐骨神经不行结扎。推拿组及阻断组自术后第4至14天，采用手套动态压力分布测量系统于“委中”穴行推拿按揉法，压力5 N、频率2 Hz，每次10 min，每日1次；阻断组与推拿时间同步按10 mg/kg予小胶质细胞阻断剂米诺环素腹腔注射，每日1次；假手术组与模型组行与推拿组相同的抓取与固定。观察各组大鼠造模前及造模第3、7、10、14天大鼠机械缩足阈值（MWT）和热缩足反射潜伏期（PWL）；采用透射电镜观察坐骨神经损伤修复情况，测量轴突直径和有髓纤维总直径，计算g-ratio值；蛋白质印迹法检测术侧脊髓背角离子钙结合适配器分子1（Iba-1）、CD206、CD68、白细胞介素10（IL-10）和β-内啡肽（β-EP）前体阿黑皮素原（POMC）蛋白水平。

结果

与假手术组同时间比较，模型组大鼠在造模第3、7、10、14天时MWT和PWL均降低（

＜0.01）；与模型组同时间比较，推拿组和阻断组在造模第10、14天时MWT和PWL均升高（

＜0.05）；与推拿组同时间比较，阻断组在造模第7、10、14天时MWT升高，在造模第10天时PWL升高（

＜0.05）。坐骨神经病理形态学显示，假手术组髓鞘结构完整、形态规则，模型组可见髓鞘崩脱、扭曲及髓鞘球，推拿组髓鞘部分形态不规则、偶见髓鞘崩脱，阻断组髓鞘部分形态不规则、磷脂脱落。与假手术组比较，模型组g-ratio值降低，脊髓背角Iba-1、CD68蛋白水平升高（

＜0.05或

＜0.01）；与模型组比较，推拿组和阻断组g-ratio值升高，推拿组和阻断组大鼠Iba-1、CD68水平降低，推拿组CD206、IL-10、POMC蛋白水平升高，阻断组CD206蛋白水平降低（

＜0.05）。

结论

推拿“委中”穴可缓解CCI模型大鼠的神经病理性疼痛，其机制可能是通过调控脊髓小胶质细胞活化，抑制其向M1型极化、促进其向M2型极化，激活IL-10/β-EP通路进而发挥镇痛效应。

Abstract

Objective

To investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms.

Methods

Thirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn.

Results

Compared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （

＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （

＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （

＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （

＜0.05 or

＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （

＜0.05）.

Conclusion

Tuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.

关键词

Keywords

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