Exogenous carbon monoxide improves postoperative anxiety-like behaviors in elderly rats by inhibiting excessive autophagy of astrocytes

Songtao WU; Jiexia WANG; Yue XIN; Weichao ZHENG; Zhiyou WU; Huitao MIAO; Limin ZHANG; Dongxue ZHANG; Shujuan LIANG

doi:10.16016/j.2097-0927.202111054

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Exogenous carbon monoxide improves postoperative anxiety-like behaviors in elderly rats by inhibiting excessive autophagy of astrocytes

Basic Medicine | 更新时间：2026-01-09

- Exogenous carbon monoxide improves postoperative anxiety-like behaviors in elderly rats by inhibiting excessive autophagy of astrocytes
- Journal of Army Medical University Vol. 44, Issue 11, Pages: 1094-1103(2022)
- 作者机构：
  
  1.075000 河北张家口，河北北方学院研究生院
  2.050017 石家庄，河北医科大学研究生院
  3.06100 河北沧州，沧州市中心医院：麻醉科
  4.06100 河北沧州，沧州市中心医院：老年内科
  5.066000 河北秦皇岛，秦皇岛市第一医院麻醉科
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81701296);the Project of Natural Science Foundation of Hebei Province(H2021110004)
- DOI：10.16016/j.2097-0927.202111054
  CLC： R619.9;R749.72;R914.3
- Received：08 November 2021，
  
  Revised：2022-01-13，
  
  Published：15 June 2022
- 稿件说明：
移动端阅览
Songtao WU, Jiexia WANG, Yue XIN, et al. Exogenous carbon monoxide improves postoperative anxiety-like behaviors in elderly rats by inhibiting excessive autophagy of astrocytes[J]. Journal of Army Medical University, 2022, 44(11): 1094-1103.
DOI：

Songtao WU, Jiexia WANG, Yue XIN, et al. Exogenous carbon monoxide improves postoperative anxiety-like behaviors in elderly rats by inhibiting excessive autophagy of astrocytes[J]. Journal of Army Medical University, 2022, 44(11): 1094-1103. DOI： 10.16016/j.2097-0927.202111054.

摘要

目的

探讨外源性一氧化碳(CO)通过抑制星形胶质细胞过度自噬改善老龄大鼠围术期应激后焦虑样行为的作用。

方法

清洁级健康雄性SD大鼠36只，分为3组(

=12): 假手术组(S组)、腹腔探查组(P组)、腹腔探查+一氧化碳释放分子-3(carbon monoxide-releasing molecule 3

CORM-3)组(PC组)。PC组大鼠在手术结束后即刻、24、48 h经尾缘静脉注射外源性CORM-3(4 mg/kg)。术后第7天采用行为学评估大鼠焦虑样行为；采用免疫荧光法评估杏仁核区神经元数量及星形胶质细胞、小胶质细胞和神经元内自噬相关蛋白B细胞淋巴瘤-2相互作用蛋白1(Bcl-2 interacting protein 1

Beclin1)和泛素(ubiquitin

Ub)的表达情况，采用Western blot法检测微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3

LC3)的表达；采用透射电镜法检测杏仁核区自噬小体的数量。

结果

旷场试验结果显示，与S组比较，P组和PC组大鼠中央区停留时间百分比明显下降，焦虑样行为增加(

0.05)；高架十字迷

宫试验表明，与S组比较，P组和PC组大鼠开放臂停留时间百分比及开放臂进入次数百分比显著下降，焦虑样行为增加(

0.05)；组织病理学结果显示，与S组比较，P组和PC组大鼠杏仁核区NeuN阳性细胞数降低(

0.05)，星形胶质细胞内Beclin1、Ub表达上调(

0.05)；Western blot检测结果显示，与S组比较，P组和PC组大鼠LC3Ⅱ/Ⅰ的比值上调(

0.05)；透射电镜下观察，S组大鼠星形胶质细胞内未见自噬小体，P组和PC组大鼠星形胶质细胞内可见自噬小体；与P组比较，PC组大鼠上述各项指标均明显改善(

0.05)。

结论

外源性CO能够改善老龄大鼠围术期应激后的焦虑样行为，其机制可能与抑制杏仁核区星形胶质细胞过度自噬相关。

Abstract

Objective

To investigate the role of exogenous carbon monoxide (CO) in improving anxiety-like behaviors in elderly rats under perioperative stress by inhibiting excessive autophagy of astrocytes.

Methods

Thirty-six clean healthy male SD rats (aged 18~20 months) were randomly divided into 3 groups (

=12): sham-operation group (Group S)

peritoneal surgery group (Group P)

and peritoneal surgery+carbon monoxide-releasing molecule 3 (CORM-3) group (Group PC). The rats in Group PC were injected with exogenous CORM-3 (4 mg/kg)

via

caudal vein immediately

and in 24 and 48 h after surgery. Open field test and elevated plus maze test were performed to evaluate the anxiety-like behaviors on the 7th day after surgery. The neuronal amount in the amygdala

the expression of Bcl-2 interacting protein 1 (Beclin 1) and ubiquitin (Ub) in the astrocytes

microglia and neurons were assessed by immunofluorescence assay. The expression levels of microtubule associated protein 1 light chain 3 (LC3) was detected by Western blotting. The number of autophagosomes in the amygdala were observed with transmission electron microscopy.

Results

The results of open field test and elevated plus maze test showed that

as compared with Group S

the percentage of staying time in the central area was significantly decreased in Group P and Group PC (

0.05)

so we

re the percentages of open arm stay duration and entry times (

0.05)

indicating increased anxiety-like behaviors in the rats from these 2 groups. The histopathological and Western blotting results suggested declined number of NeuN positive cells in the amygdala

up-regulated expression of Beclin 1 and Ub in the astrocytes

and elevated ratio of LC3Ⅱ/Ⅰ were observed in Group P and PC (

0.05). Under transmission electron microscope

no autophagosomes were found in the astrocytes of Group S

while they were observed in Group P and PC. However

the above indexes of Group PC were all remarkably improved in comparison with those of Group P (

0.05).

Conclusion

Exogenous CO can improve the anxiety-like behaviors in aged rats under perioperative stress

and the mechanism may be associated with its inhibition on excessive autophagy of astrocytes in the amygdala.

关键词

Keywords

references

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