榄香烯乳状注射液通过抑制SNI大鼠脊髓背角星形胶质细胞的活化和NDRG2的表达来缓解疼痛

Li-tian MA; Yang BAI; Jie LI; Yu QIAO; Yang LIU; Jin ZHENG

doi:10.1007/s11655-021-3438-3

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榄香烯乳状注射液通过抑制SNI大鼠脊髓背角星形胶质细胞的活化和NDRG2的表达来缓解疼痛

Original Article | Updated：2021-11-29

- 榄香烯乳状注射液通过抑制SNI大鼠脊髓背角星形胶质细胞的活化和NDRG2的表达来缓解疼痛
- Elemene Emulsion Injection Administration Reduces Neuropathic Pain by Inhibiting Astrocytic NDRG2 Expression within Spinal Dorsal Horn^*
- Chinese Journal of Integrative Medicine 2021年27卷第12期页码：912-918
- Affiliations：
  
  1.Department of Traditional Chinese Medicine, Tangdu Hospital,the Fourth Military Medical University, Xi'an (710038), China
  2.Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xi'an (710032), China
  3.Department of Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, the Fourth Military Medical University, Xi'an (710032),China
  4.Department of Neurosurgery, General Hospital of Northern Theater Command (General Hospital of Shenyang Military Command), Shenyang (110016), China
  5.Department of Endocrinology, Xijing Hospital, the Fourth Military Medical University, Xi'an (710038), China
  6.Laser Medical Center, Hainan Hospital, People's Liberation Army General Hospital, Sanya(572013), Hainan Province, China
  7.Health Center of 31658 of the People's Liberation Army, Xining (810000), China
- Author bio：
  
  Prof. ZHENG Jin, E-mail: zjddln@163.com
- Funds：
  
  the Science and Technology Co-ordination Innovation Project Plan of Shaanxi Province(2016KTCL03-16)
- DOI：10.1007/s11655-021-3438-3
  中图分类号：
- 纸质出版日期：2021-11-15，
  
  网络出版日期：2021-01-09，
  
  录用日期：2020-09-28
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Li-tian MA, Yang BAI, Jie LI, 等. 榄香烯乳状注射液通过抑制SNI大鼠脊髓背角星形胶质细胞的活化和NDRG2的表达来缓解疼痛[J]. Chinese Journal of Integrative Medicine, 2021,27(12):912-918.

Li-tian MA, Yang BAI, Jie LI, et al. Elemene Emulsion Injection Administration Reduces Neuropathic Pain by Inhibiting Astrocytic NDRG2 Expression within Spinal Dorsal Horn^*[J]. Chinese Journal of Integrative Medicine, 2021,27(12):912-918.
Li-tian MA, Yang BAI, Jie LI, 等. 榄香烯乳状注射液通过抑制SNI大鼠脊髓背角星形胶质细胞的活化和NDRG2的表达来缓解疼痛[J]. Chinese Journal of Integrative Medicine, 2021,27(12):912-918. DOI： 10.1007/s11655-021-3438-3.

Li-tian MA, Yang BAI, Jie LI, et al. Elemene Emulsion Injection Administration Reduces Neuropathic Pain by Inhibiting Astrocytic NDRG2 Expression within Spinal Dorsal Horn^*[J]. Chinese Journal of Integrative Medicine, 2021,27(12):912-918. DOI： 10.1007/s11655-021-3438-3.

摘要

目的:

榄香烯乳状注射液(以下简称榄香烯) 对大鼠坐骨神经分支损伤模型(Spared nerve injury

SNI) 镇痛机制的研究.

方法:

65只大鼠被随机分成5组: 空白组

假手术组

SNI组

SNI+榄香烯组

假手术组+榄香烯组. 建立大鼠SNI模型

并腹腔注射榄香烯40 mg/kg/d

连续给药14 d. 用大鼠缩足阈值(PWT) 评价药物的镇痛作用; 用高架十字迷宫实验(Evaluated-plus maze

EPM) 评价榄香烯对大鼠焦虑情绪的影响; 并用免疫组化、蛋白免疫印迹和双标免疫荧光技术检测腰膨大处脊髓背角的胶质纤维酸性蛋白(GFAP) 及NDRG2蛋白的表达情况.

结果:

PWT及EPM结果显示: SNI模型建模成功

SNI大鼠的缩足阈值以及在迷宫中的探索行为显著下降; 40 mg/kg/d的榄香烯连续给药14 d可以显著提高SNI模型大鼠的机械痛阈

改善大鼠焦虑情绪; 免疫组化、蛋白免疫印迹及双标免疫荧光技术表明: 榄香烯可以显著抑制SNI大鼠脊髓背角的星形胶质细胞的活化以及NDRG2的表达.

结论:

40 mg/Kg/d的榄香烯连续给药14 d可以显著缓解大鼠的神经病理性痛

其机制可能是抑制大鼠腰膨大脊髓背角的星形胶质细胞的活化及NDRG2的表达来实现的.

Abstract

Objective:

To investigate the mechanisms underlying elemene-induced analgesia in rats with spared nerve injury (SNI).

Methods:

Sixty-five rats were equally divided into 5 groups using a random number table: naive group

sham group

SNI group

SNI + elemene (40 mg•kg

-1

•d

-1

) group and naive + elemene (40 mg•kg

-1

•d

-1

) group. An SNI rat model was established and the intervention were given respectively for 14 consecutive days. Von Frey filament tests and elevated plus-maze (EPM) tests were used to evaluate the effect of elemene on the mechanical threshold and anxiety

respectively. Immunoblotting and immunostaining were used to measure the expression of glial fibrillary acidic protein (GFAP) and NMYC downstream-regulated gene 2 (NDRG2) within the lumbar spinal dorsal horn (SDH).

Results:

The SNI rat model exhibited a significant decrease in paw withdrawal threshold and exploratory behaviour in the EPM (

0.05). Consecutive administration of elemene alleviated SNI-induced mechanical allodynia and anxiety in rats (

0.05). Immunohistochemical data showed that elemene decreased SNI-induced upregulation of NDRG2 within the SDH (

0.05). Double immunofluorescent staining data further showed that elemene decreased SNI-induced upregulation of the number of GFAP immunoreactive (-ir)

NDRG-ir

and GFAP/NDRG2 double-labelled cells within the SDH (

0.05). Immunoblotting data showed that elemene decreased SNI-induced upregulation of GFAP and NDRG2 within the SDH (

0.05).

Conclusion:

Elemene possibly alleviated neuropathic pain by downregulating the expression of NDRG2 in spinal astrocytes in a rat model of SNI.

关键词

Keywords

elemene emulsion injectionastrocyteNMYC downstream-regulated gene 2

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