Effect of Celastrol on Neuropathic Pain Model Mice

Hong-yan WU; Yu-qi SHI; Jia-hao LI; Chun-yan ZHU; Na LIN

doi:10.13422/j.cnki.syfjx.20201437

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Effect of Celastrol on Neuropathic Pain Model Mice

Pharmacology | 更新时间：2020-08-11

- Effect of Celastrol on Neuropathic Pain Model Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 13, Pages: 97-103(2020)
- 作者机构：
  
  中国中医科学院中药研究所，北京 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201437
  CLC： R2-0;R289;R285.5
- Published Online：16 April 2020，
  
  Published：05 July 2020
- 稿件说明：
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吴红艳,师钰琪,李佳豪等.雷公藤红素对神经病理性疼痛模型小鼠的干预作用[J].中国实验方剂学杂志,2020,26(13):97-103.

WU Hong-yan,SHI Yu-qi,LI Jia-hao,et al.Effect of Celastrol on Neuropathic Pain Model Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(13):97-103.
吴红艳,师钰琪,李佳豪等.雷公藤红素对神经病理性疼痛模型小鼠的干预作用[J].中国实验方剂学杂志,2020,26(13):97-103. DOI： 10.13422/j.cnki.syfjx.20201437.

WU Hong-yan,SHI Yu-qi,LI Jia-hao,et al.Effect of Celastrol on Neuropathic Pain Model Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(13):97-103. DOI： 10.13422/j.cnki.syfjx.20201437.

摘要

目的

观察雷公藤红素对神经病理性疼痛（NP）模型小鼠疼痛、焦虑及抑郁共病的干预作用以及初步机制探索。

方法

将小鼠随机分为假手术组，模型组，普瑞巴林组（25 mg·kg

-1

），雷公藤红素低、中、高剂量组（5，10，20 mg·kg

-1

），以L5脊神经结扎（SNL）的方法制备NP小鼠模型，采用Von Frey法检测小鼠机械痛阈值，旷场和悬尾实验分别检测小鼠焦虑和抑郁症状，免疫组化（IHC）观察各组小鼠海马小胶质细胞形态的变化；选用BV2-TdT小胶质细胞，以1 mg·L

-1

脂多糖（LPS）诱导细胞炎症，分为正常组、模型组、雷公藤红素（100 nmol·L

-1

）组，采用实时荧光定量聚合酶链式反应（Real-time PCR）检测肿瘤坏死因子-

（TNF-

）的mRNA表达，免疫荧光（IF）检测TNF-

的蛋白表达。

结果

与假手术组比较，SNL模型组小鼠具有显著的机械痛敏、焦虑和抑郁症状（

0.05，

0.01），且海马小胶质细胞胞体面积明显升高（

0.05），呈阿米巴样；与SNL模型组比较，20 mg·kg

-1

雷公藤红素能明显升高SNL小鼠50%缩足阈值和旷场中央区停留时间（

0.05，

0.01），降低SNL小鼠悬尾不动时间（

0.05），减少SNL小鼠海马小胶质细胞的胞体面积（

0.05）。体外实验显示，与正常组比较，LPS诱导BV2小胶质细胞后2~4 h，细胞TNF-

的mRNA和蛋白表达均明显升高(

0.05，

0.01)；与LPS组比较，100 nmol·L

-1

雷公藤红素能显著抑制LPS诱导的TNF-

在mRNA和蛋白水平上表达的异常升高（

0.01）。

结论

雷公藤红素能改善NP模型小鼠痛与情绪障碍共病，其机制可能与中枢神经免疫调控有关。

Abstract

Objective

To investigate the effect of celastrol on painful and the emotional of anxiety and depression comorbidity on neuropathic pain model animal and to explore its possible mechanism．

Method

Mice were randomly divided into sham group， model group， pregabalin group(25 mg·kg

-1

)， low， medium and high-dose celastrol groups (5，10，20 mg·kg

-1

). The mice model of neuropathic pain were established by the L5 spinal nerve ligation (SNL). After successful modeling， the treatment groups were given intragastric administration， the sham group and the model group were given the same volume of warm water.Mechanical pain were detected by Von Frey tests， anxiety and depression behaviors were separately detected by the open field and the tail tailing experiments， the pathological changes of microglial cells in hippocampus of mice in each group were observed by immunohistochemical staining (IHC). The inflammation of BV2 microglial cell made by 1 mg·L

-1

lipopolysaccharide (LPS). Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-

(TNF-

). The expression levels of TNF-

protein were detected by immunofluorescence（IF） staining.

Result

Compared with sham group， significant change of mechanical pain thresholds， anxiety and depression were detected in the SNL mice (

0.05，

0.01)， the significant decreases of the body size of hippocampal microglia (

0.05). Compared with SNL model group， 20 mg·kg

-1

celastrol significantly increased the 50% paw withdraw threshold and the time of the open feld tests (

0.05，

0.01)，and decreased the time of the tail tailing experiments in the SNL mice (

0.05)， and the cell body area of hippocampal microglia in SNL mice was reduced (

0.05). Experiment in vitro show， compared with control group， the expression of TNF-

mRNA and protein expression in LPS-induced BV2 microglia increased significantly from 2-4 h (

0.05，

0.01). Compared with the LPS group， after 100 nmol·L

-1

celastrol administration， LPS-induced microglia inflammatory factor TNF-

mRNA and TNF-

protein expression were significantly decreased (

0.01).

Conclusion

Celastrol can relieve pain-emotion comorbidity on neuropathic pain model mice， and its mechanism may be related to the anti-inflammation in the central nerves system.

关键词

Keywords

references

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