Effect and mechanism of ginsenoside Rg1 in alleviating neuropathic pain in rats

Guo Qiang; Wang Kun; Dang Caiyan; Gao Xiaomeng

doi:10.13406/j.cnki.cyxb.003839

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Effect and mechanism of ginsenoside Rg1 in alleviating neuropathic pain in rats

Basic research | 更新时间：2025-10-21

- Effect and mechanism of ginsenoside Rg1 in alleviating neuropathic pain in rats
- Journal of Chongqing Medical University Vol. 50, Issue 10, Pages: 1418-1425(2025)
- 作者机构：
  
  西安市中心医院疼痛科，西安 710004
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003839
  CLC： R285.5;R741
- Received：12 October 2024，
  
  Revised：2025-02-19，
  
  Accepted：07 February 2025，
  
  Published：28 October 2025
- 稿件说明：
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郭强,王坤,党彩艳,等.人参皂苷Rg1对大鼠神经病理性疼痛的缓解作用和机制研究[J].重庆医科大学学报,2025,50(10):1418-1425.

Guo Qiang,Wang Kun,Dang Caiyan,et al.Effect and mechanism of ginsenoside Rg1 in alleviating neuropathic pain in rats[J].Journal of Chongqing Medical University,2025,50(10):1418-1425.
郭强,王坤,党彩艳,等.人参皂苷Rg1对大鼠神经病理性疼痛的缓解作用和机制研究[J].重庆医科大学学报,2025,50(10):1418-1425. DOI： 10.13406/j.cnki.cyxb.003839.

Guo Qiang,Wang Kun,Dang Caiyan,et al.Effect and mechanism of ginsenoside Rg1 in alleviating neuropathic pain in rats[J].Journal of Chongqing Medical University,2025,50(10):1418-1425. DOI： 10.13406/j.cnki.cyxb.003839.

摘要

目的

探讨人参皂苷Rg1（ginsenoside Rg1，GRg1）在大鼠神经病理性疼痛中的作用和镇痛机制。

方法

将30只成年SD雄性大鼠随机分为5组：假手术组（sham）、模型组（SNI）、GRg1干预组（GRg1）、GRg1+空载质粒干预组（GRg1+vector）、GRg1+TLR4过表达质粒干预组（GRg1+TLR4），每组6只。后4组采用坐骨神经分支选择性损伤（spared nerve injury，SNI）法建立神经病理性疼痛大鼠模型，模型制备成功后以GRg1灌胃治疗14 d，尾静脉注射质粒。sham组仅暴露坐骨神经，不进行任何损伤操作。使用机械疼痛检测仪和辐射热测痛仪分别检测大鼠术前1 d 和术后1、3、7、14 d 的机械缩足反射阈值和热缩足反射潜伏期；取大鼠L

脊髓组织，通过实时荧光定量PCR、蛋白免疫印迹法和间接免疫荧光实验检测星形胶质细胞活化标志物GFAP和小胶质细胞标志物Iba-1的mRNA和蛋白表达水平；酶联免疫吸附实验测定脊髓组织中IL-1β、TNF-α和CXCL1的含量；比色法测定脊髓组织中NO的含量；分子对接技术探究GRg1与TLR4的结合能力和相互作用模式。

结果

GRg1恢复SNI大鼠机械缩足反射阈值（F=24.67，P=0.000）和热缩足反射潜伏期（

=8.058，

=0.034），同时下调SNI大鼠脊髓组织中GFAP（mRNA：

=37.74，P=0.000；蛋白：F=98.71，P=0.001）和Iba-1（mRNA：

=62.11，

=0.000；蛋白：

=187.0，

=0.000）的表达水平；GRg1降低SNI大鼠脊髓组织中IL-1β（

=56.96，

=0.000）、TNF-α（

=55.25，

=0.000）、CXCL1（

=93.54，

=0.000）和NO（

=30.57，

=0.000）含量

。机制研究发现GRg1与TLR4结合高度稳定；GRg1下调SNI大鼠脊髓组织中TLR4表达水平（mRNA：

=62.66，

=0.000；蛋白：

=53.52，

=0.000），以及p38（

=300.3，

=0.000）和p65（

=121.6，

=0.000）磷酸化水平；TLR4的过表达逆转GRg1的作用（机械缩足反射阈值：

=24.67，

=0.000；热缩足反射潜伏值：

=8.058，

=0.034；GFAP，mRNA：

=37.74，

=0.009；蛋白：

=98.71，

=0.000；Iba-1，mRNA：

=62.11，

=0.006；蛋白：

=187.0，

=0.000；IL-1β：

=56.96，

=0.006；TNF-α：

=55.25，

=0.000；CXCL1：

=93.54，

=0.000；NO：

=30.57，

=0.042；TLR4，mRNA：

=62.66，

=0.000；蛋白：

=53.52，

=0.000；p38磷酸化水平：

=300.3，

=0.000；p65磷酸化水平：

=121.6，

=0.000）。

结论

GRg1可能通过调控TLR4-p38/MAPK-NF-κB通路抑制大鼠脊髓组织中星形胶质细胞和小胶质细胞活化，从而对SNI大鼠产生镇痛作用。

Abstract

Objective

To investigate the role and analgesic mechanism of ginsenoside Rg1（GRg1） in neuropathic pain in rats.

Methods

A total of 30 adult male Sprague-Dawley rats were randomly divided into sham-operation group，spared nerve injury（SNI） group，GRg1 group，GRg1+empty vector group（GRg1+vector group），and GRg1+TLR4 overexpression plasmid group（GRg1+TLR4 group），with 6 rats in each group. The SNI method was used to establish a rat model of neuropathic pain in the latter four groups，and after successful modeling，GRg1 was given by gavage for 14 days，while the plasmid was injected via the caudal vein. The sciatic nerve was exposed for the sham-operation group without any injury manipulation. A mechanical pain threshold det

ector and a radiation thermal pain threshold detector were used to measure mechanical withdrawal threshold and thermal withdrawal latency on day 1 before surgery and on days 1，3，7，and 14 after surgery. L

-L

spinal cord tissue samples were collected，and quantitative real-time PCR，Western blot，and indirect immunofluorescence assay were used to measure the mRNA and protein expression levels of GFAP，a marker for astrocyte activation，and Iba-1，a marker for microglial cells；ELISA was used to measure the content of IL-1β，TNF-α，and CXCL1 in spinal cord tissue，and colorimetry was used to measure the content of NO in spinal cord tissue；molecular docking was used to investigate the binding ability and interaction mode between GRg1 and TLR4.

Results

GRg1 restored mechanical withdrawal threshold（

=24.67，

=0.000） and thermal withdrawal latency in SNI rats （

=8.058，

=0.034） and downregulated the expression levels of GFAP（mRNA：

=37.74，

=0.000；protein：

=98.71，

=0.001） and Iba-1（mRNA：

=62.11，

=0.000；protein：

=187.0，

=0.000） in spinal cord tissues of SNI rats，and it also reduced the levels of IL-1β（

=56.96，

=0.000），TNF-α（

=55.25，

=0.000），CXCL1（

=93.54，

=0.000） and NO（

=30.57，

=0.000） in the spinal cord tissues of SNI rats. The study on mechanisms showed highly stable binding between GRg1 and TLR4，and GRg1 downregulated the expression level of TLR4（mRNA：

=62.66，

=0.000； protein：

=53.52，

=0.000） and the phosphorylation levels of p38（

=300.3，

=0.000） and p65（

=121.6，

=0.000） in spinal cord tissues of SNI rats ，wher

eas the overexpression of TLR4 reversed the effect of GRg1（Mechanical Paw Withdrawal Threshold：

=24.67，

=0.000；Thermal Paw Withdrawal Latency：

=8.058，

=0.034；GFAP，mRNA：

=37.74，

=0.009；Protein：

=98.71，

=0.000；Iba-1，mRNA：

=62.11，

=0.006；Protein：

=187.0，

=0.000；IL-1β：

=56.96，

=0.006；TNF-α：

=55.25，

=0.000；CXCL1：

=93.54，

=0.000；NO：

=30.57，

=0.042；TLR4， mRNA：

=62.66，

=0.000；Protein：

=53.52，

=0.000；p38 Phosphorylation Level：

=300.3，

=0.000；p65 Phosphorylation Level：

=121.6，

=0.000）.

Conclusion

GRg1 may exert an analgesic effect on SNI rats by regulating the TLR4-p38/MAPK-NF-κB signaling pathway and activating the activation of astrocytes and microglial cells in spinal cord tissue.

关键词

Keywords

references

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