Improvement effect and mechanism of sanguinarine on inflammatory pain in rats with lumbar disc herniation

RUAN Zhen; HE Shenghua; GONG Xuehua; QIAO Song; WANG Chao

doi:10.6039/j.issn.1001-0408.2024.09.11

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Improvement effect and mechanism of sanguinarine on inflammatory pain in rats with lumbar disc herniation

更新时间：2025-09-25

- Improvement effect and mechanism of sanguinarine on inflammatory pain in rats with lumbar disc herniation
- ZHONGGUO YAOFANG Vol. 35, Issue 9, Pages: 1087-1093(2024)
- 作者机构：
  
  1.武汉市中医医院推拿科，武汉　430000
  2.武汉市第七医院中南路街第一社区卫生服务中心，武汉　430060
  3.湖北省中西医结合医院康复医学中心推拿科，武汉　430010
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.09.11
  CLC： R965
- Received：29 November 2023，
  
  Revised：2024-03-21，
  
  Accepted：31 March 2024，
  
  Published：15 May 2024
- 稿件说明：
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阮祯,何生华,龚雪花,等.血根碱对腰椎间盘突出症大鼠炎性疼痛的改善作用及机制[J].中国药房,2024,35(09):1087-1093.

RUAN Zhen,HE Shenghua,GONG Xuehua,et al.Improvement effect and mechanism of sanguinarine on inflammatory pain in rats with lumbar disc herniation[J].ZHONGGUO YAOFANG,2024,35(09):1087-1093.
阮祯,何生华,龚雪花,等.血根碱对腰椎间盘突出症大鼠炎性疼痛的改善作用及机制[J].中国药房,2024,35(09):1087-1093. DOI： 10.6039/j.issn.1001-0408.2024.09.11.

RUAN Zhen,HE Shenghua,GONG Xuehua,et al.Improvement effect and mechanism of sanguinarine on inflammatory pain in rats with lumbar disc herniation[J].ZHONGGUO YAOFANG,2024,35(09):1087-1093. DOI： 10.6039/j.issn.1001-0408.2024.09.11.

摘要

目的

研究血根碱（SG）对腰椎间盘突出症（LDH）大鼠炎性疼痛的改善作用及机制。

方法

制备LDH模型大鼠，然后分为模型组和SG低、中、高剂量组（1.00、2.50、6.25 mg/kg）以及SG高剂量+Anisomycin[丝裂原活化蛋白激酶（MAPK）激活剂]组（6.25 mg/kg SG+5 mg/kg Anisomycin），每组10只；另取10只大鼠作为对照组。各组大鼠腹腔注射相应药物，对照组和模型组大鼠腹腔注射等体积生理盐水，每天1次，连续7 d。观察大鼠一般情况及神经功能变化；测定大鼠疼痛阈值[包括机械刺激缩足反射阈值（PWMT）和热刺激缩足反射潜伏期（PWTL）]；观察大鼠背根神经节（DRG）组织病理变化；检测大鼠血清中炎症因子[肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）]和疼痛因子[神经肽Y（NPY）、5羟色胺（5-HT）]水平；观察脊髓小胶质细胞中离子钙接头蛋白1（Iba-1）和星形胶质细胞中胶质原纤维酸性蛋白（GFAP）的阳性表达；检测大鼠DRG组织中MAPK/胞外信号调节激酶（ERK）/核因子κB（NF-κB）信号通路相关蛋白和TNF-α、IL-1β蛋白的表达。

结果

与对照组相比，模型组大鼠精神食欲不振，后肢运动障碍，DRG椎间盘神经元细胞排列紊乱；神经功能评分，血清中TNF-α、IL-1β、NPY水平，Iba-1、GFAP阳性表达，DRG组织中p38 MAPK、ERK1/2、NF-κB p65蛋白磷酸化水平和TNF-α、IL-1β蛋白表达水平均显著升高（

＜0.05）；PWMT、PWTL和血清中5-HT水平均显著降低（

＜0.05）。与模型组相比，SG各剂量组大鼠精神食欲好转，后肢运动障碍缓解，DRG椎间盘神经元结构改善，上述定量指标水平均显著逆转（

＜0.05）。Anisomycin可逆转SG对LDH大鼠炎性疼痛的改善作用。

结论

SG可通过抑制LDH大鼠DRG组织中小胶质细胞活化，减少炎症因子释放，提高疼痛阈值，从而改善炎性疼痛；其作用机制可能与抑制MAPK/ERK/NF-κB信号通路有关。

Abstract

OBJECTIVE

To study the improvement effect and mechanism of sanguinarine （SG） on inflammatory pain in rats with lumbar disc herniation （LDH） and its mechanism.

METHODS

LDH model rats were established and divided into model group， SG low-dose， medium-dose and high-dose groups （1.00， 2.50， 6.25 mg/kg）， high-dose of SG+Anisomycin [mitogen-activated protein kinase （MAPK） activator] group （6.25 mg/kg SG+5 mg/kg Anisomycin）， with 10 rats in each group. Another 10 rats were included as the control group. Each group was given corresponding drugs intraperitoneally， while the control group and model group were given an equal volume of normal saline intraperitoneally， once a day， for 7 consecutive days. The general situation and neurological changes of rats in each group were observed， and the pain threshold [including paw withdrawal mechanical threshold （PWMT） and paw withdrawal thermal latency （PWTL）] of rats was determined； the histopathological changes of dorsal root ganglion （DRG） were observed in rats. The serum levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）] and pain factors [neuropeptide Y （NPY）， 5-hydroxytryptamine （5-HT）] in rats were detected. The positive expressions of ionized-calcium binding adaptor molecule-1 （Iba-1） in spinal cord microglia and glial fibrillary acidic protein （GFAP） in astrocytes were observed. The expressions of proteins related to MAPK/extracellular signal-regulated kinase （ERK）/nuclear factor κB （NF-κB） signaling pathway， TNF-α and IL-1β proteins were detected in DRG tissue of rats.

RESULTS

Compared with the control group， the rats in the model group showed decreased appetite， hindlimb movement disorders， and disordered neuronal cell arrangement， the neurological score， the levels of TNF-α， IL-1β， NPY， the positive expressions of Iba-1 and GFAP， the phosphorylations of p38 MAPK， ERK1/2 and NF-κB p65， the protein expressions of TNF-α and IL-1β were significantly increased （

＜0.05）； PWMT， PWTL and the levels of 5-HT were significantly reduced （

＜0.05）. Compared with the model group， the rats of SG groups showed some relief in their mental appetite and hindlimb motor disorders， the intervertebral disc structure of DRG was restored， and the levels of the above quantitative indicators had significantly reversed （

＜0.05）. Anisomycin reversed the improvement effect of SG on inflammatory pain in LDH rats.

CONCLUSIONS

SG can improve inflammatory pain by inhibiting the activation of microglia in DRG tissue of LDH rats， reducing the release of inflammatory factors， and increasing pain threshold， and its mechanism of action may be related to the inhibition of MAPK/ERK/NF-κB signaling pathway.

关键词

Keywords

references

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