大麻素受体2激动剂AM1241抑制大鼠脊髓损伤后纤维瘢痕形成

凌成明; 储卫华; 袁继超; 陈欣; 刘静静; 张洪燕; 林江凯

doi:10.16016/j.2097-0927.202202141

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大麻素受体2激动剂AM1241抑制大鼠脊髓损伤后纤维瘢痕形成

神经科学 | 更新时间：2026-01-09

- 大麻素受体2激动剂AM1241抑制大鼠脊髓损伤后纤维瘢痕形成
- Cannabinoid receptor 2 agonist AM1241 inhibits fibrous scarring after spinal cord injury in rats
- 陆军军医大学学报 2022年44卷第10期页码：991-1000
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)第一附属医院神经外科
  2.400038 重庆，陆军军医大学(第三军医大学)第一附属医院神经内科
  3.614000 四川乐山，武警四川省总队医院神经外科
- 作者简介：
  
  [林江凯，E-mail: jklin@tmmu.edu.cn LIN Jiangkai, E-mail: jklin@tmmu.edu.cn
- 基金信息：
  
  国家自然科学基金面上项目(81571214);重庆市技术创新与应用示范项目(cstc2018jscx-msybX0092);利益冲突声明所有作者声明不存在利益冲突。
- DOI：10.16016/j.2097-0927.202202141
  中图分类号： R364.31;R651.2;R977.6
- 收稿：2022-02-24，
  
  修回：2022-03-16，
  
  纸质出版：2022-05-30
- 稿件说明：
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凌成明, 储卫华, 袁继超, 等. 大麻素受体2激动剂AM1241抑制大鼠脊髓损伤后纤维瘢痕形成[J]. 陆军军医大学学报, 2022,44(10):991-1000.

Chengming LING, Weihua CHU, Jichao YUAN, et al. Cannabinoid receptor 2 agonist AM1241 inhibits fibrous scarring after spinal cord injury in rats[J]. Journal of Army Medical University, 2022, 44(10): 991-1000.
凌成明, 储卫华, 袁继超, 等. 大麻素受体2激动剂AM1241抑制大鼠脊髓损伤后纤维瘢痕形成[J]. 陆军军医大学学报, 2022,44(10):991-1000. DOI： 10.16016/j.2097-0927.202202141.

Chengming LING, Weihua CHU, Jichao YUAN, et al. Cannabinoid receptor 2 agonist AM1241 inhibits fibrous scarring after spinal cord injury in rats[J]. Journal of Army Medical University, 2022, 44(10): 991-1000. DOI： 10.16016/j.2097-0927.202202141.

摘要

目的

探讨AM1241对大鼠脊髓损伤后纤维瘢痕形成的作用及其机制。

方法

选取雌性6~8周龄Sprague-Dawley大鼠144只，分为4组：①假手术组(

=24)只移除椎板以暴露硬脊膜，不切开硬脊膜，术后给予生理盐水3 mL/kg；②载体组(

=40)建立大鼠脊髓背侧半切损伤模型，术后给予生理盐水3 mL/kg；③AM1241组(

=40)在载体组基础上给予大麻素受体2(cannabinoid receptor 2，CBR2)激动剂(AM1241，3 mg/kg) 治疗；④AM1241+AM630组(

=40)在术后AM1241治疗前30 min给予CBR2拮抗剂(AM630，3 mg/kg)。各组药物均腹腔注射，1次/d，连续14 d。采用免疫荧光染色、Western blot、ELISA等方法评估AM1241对大鼠纤维瘢痕形成的抑制作用，同时采用行为学、电生理检测AM1241对大鼠神经功能的影响。

结果

与载体组比较，AM1241组大鼠脊髓损伤后，主要纤维瘢痕成分的表达降低，脊髓损伤后，纤维瘢痕面积减少，给予CBR2拮抗剂AM630后逆转了上述现象，差异均有统计学意义(

0.05)。tubulin βⅢ免疫荧光染色、行为学评估、电生理实验结果显示：AM1241组促进了脊髓神经元细胞的存活，改善了脊髓损伤后的神经功能，包括Basso-Beattie-Bresnahan(BBB)评分[载体组(15.38±0.38)

AM1241组(18.38±0.50)

AM1241+AM630组(15.50±0.33)，

0.05

]

、斜板实验角度[载体组(54.25±1.25)°

AM1241组(64.25±1.05)°

AM1241+AM630组(54.75±0.49)°，

0.05

]

等；ELISA实验结果显示：AM1241组抑制M1型巨噬细胞标记物iNOS、TNF-α、IL-1β的表达(

0.05)，增强M2型巨噬细胞标记物CD206、Arg-1的表达(

0.05)，降低促纤维化因子TGF-β1的表达(

0.01)；而应用CBR2拮抗剂AM630后逆转了上述作用。

结论

刺激大鼠CBR2能减少脊髓损伤后纤维瘢痕、改善神经功能，这一作用可能是通过影响巨噬细胞极化来实现的。

Abstract

Objective

To determine the role of cannabinoid receptor 2 (CBR2) agonist

AM1241

in the formation of fibrous scars in rats after spinal cord injury and elucidate the underlying mechanism.

Methods

A total of 144 female Sprague-Dawley rats were selected an

d divided into 4 groups: sham operation group (

=24

only the lamina was removed to expose the dura mater

and 3 mL/kg normal saline was given postoperatively)

vehicle group (

=40

the rats was inflicted to establish a model of dorsal hemisection and then given 3 mL/kg of normal saline)

AM1241 group (

=40

the rats were given 3 mg/kg AM1241 on the basis of the vehicle group)

and AM1241+AM630 group (

=40

after modeling

the rats were given 3 mg/kg AM630

CBR2 antagonist

in 30 min before AM1241 treatment). The corresponding drugs were injected intraperitoneally to each group

once a day

for 14 consecutive days. Immunofluorescence staining

Western blotting and ELISA were performed to evaluate the inhibitory effects of AM1241 on fibrous scar formation

and behavioral electrophysiology were carried out to detect its effect on neurological function.

Results

After spinal cord injury

AM1241 significantly reduced the expression of the main molecules in fibrous scars

as well as the area of fibrous scar

while the treatment of AM630 reversed above phenomena

with statistical significances (

0.05). The results of tubulin βⅢ immunofluorescence staining

behavioral assessment as well as electrophysiological experiments demonstrated that AM1241 could promote the survival of spinal cord neurons

improve neurological function after injury

such as Basso-Beattie-Bresnahan(BBB) score and angle of oblique board test [vehicle group

AM1241 group

AM1241+AM630 group: 15.38±0.38

18.38± 0.50

15.50±0.33

0.05; (54.25±1.25)°

(64.25±1.05)°

(54.75±0.49)°

0.05

]

. ELISA indicated that AM1241 inhibited the expression of iNOS

TNF-α and IL-1β (markers of M1-type macrophages

0.01)

enhanced the expression of CD206 and Arg-1 (ma

rkers of M2-type macrophages

0.05)

and decreased the expression of TGF-β1 (fibrogenic factor

0.01). The treatment of CBR2 antagonist

AM630 led to opposite results.

Conclusion

Stimulation of CBR2 decreases fibrous scarring and improves neurological function after spinal cord injury in rats

which might be attained by influencing macrophage polarization.

关键词

Keywords

references

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