Protective effect of dexmedetomidine on intestinal barrier function in septic rats

Shijie ZHOU; Li WANG; Liangming LIU; Tao LI; Hong YAN

doi:10.16016/j.2097-0927.202205043

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Protective effect of dexmedetomidine on intestinal barrier function in septic rats

Monographic Reports: Treatment of war wound and traumatic shock | 更新时间：2026-01-09

- Protective effect of dexmedetomidine on intestinal barrier function in septic rats
- Journal of Army Medical University Vol. 44, Issue 20, Pages: 2061-2067(2022)
- 作者机构：
  
  1.400042 重庆，陆军特色医学中心：麻醉科
  2.400042 重庆，陆军特色医学中心：战伤休克与输血研究室，创伤、烧伤与复合伤国家重点实验室
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202205043
  CLC： R322.45;R631.2;R971.93
- Received：10 May 2022，
  
  Revised：2022-07-18，
  
  Published：30 October 2022
- 稿件说明：
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Shijie ZHOU, Li WANG, Liangming LIU, et al. Protective effect of dexmedetomidine on intestinal barrier function in septic rats[J]. Journal of Army Medical University, 2022, 44(20): 2061-2067.
DOI：

Shijie ZHOU, Li WANG, Liangming LIU, et al. Protective effect of dexmedetomidine on intestinal barrier function in septic rats[J]. Journal of Army Medical University, 2022, 44(20): 2061-2067. DOI： 10.16016/j.2097-0927.202205043.

摘要

目的

探讨右美托咪定对脓毒症大鼠肠道屏障的保护作用。

方法

采用盲肠结扎穿孔(cecal ligation and puncture，CLP)构建大鼠脓毒症模型。将SD大鼠按随机数字表法分为假手术(Sham) 组、脓毒症(sepsis，Sep)组、常规治疗(conventional treatment，Ct)组、右美托咪定治疗(dexmedetomidine，Dex)组；观察不同处理组大鼠存活率及存活时间、肠道通透性、血二胺氧化酶(diamine oxidase，DAO)、前炎症细胞因子(TNF-α、IL-1β)水平、肠组织病理结构和肠道巨噬细胞M1型表型情况。培养离体巨噬细胞，根据处理方式不同分为正常对照(Control)组、脂多糖(lipopolysaccharide，LPS)组、Dex组，观察右美托咪定对LPS刺激后对M1型巨噬细胞表型的影响。

结果

与假手术组比较，脓毒症组大鼠存活率和存活时间显著降低(

0.01)、肠道通透性和血中前炎症细胞因子明显升高(

0.01)，肠组织损伤严重，表现为肠绒毛萎缩、断裂，红细胞和炎性细胞浸润明显，肠道巨噬细胞iNOS表达增加；常规治疗组大鼠存活时间较脓毒症组有所延长，肠道通透性和血中前炎症细胞因子降低不明显，肠病理结构改善不显著，iNOS表达未见

明显减少；与常规治疗组比较，右美托咪定组大鼠存活时间和存活率显著提高(

0.05)，肠道通透性和血清前炎症细胞因子显著降低(

0.01)，肠病理结构明显改善，iNOS表达减少。细胞实验结果显示：LPS刺激后，巨噬细胞M1型表型增多，iNOS表达明显增多，TNF-α释放显著增加(

0.01)；与LPS组比较，右美托咪定组巨噬细胞iNOS表达明显减少，TNF-α a水平显著下降(

0.05)。

结论

右美托咪定能保护脓毒症大鼠肠道屏障功能，其机制可能与通过抑制巨噬细胞M1表型、抑制炎症反应有关。

Abstract

Objective

To investigate the protective effect of dexmedetomidine (DEX) on intestinal barrier in septic rats.

Methods

Rat model of sepsis was induced by cecal ligation and puncture (CLP). SD rats were randomly divided into 4 groups: sham operation group

sepsis group

conventional treatment group and DEX group. The survival rate

survival time and blood levels of pro-inflammatory cytokines (TNF-α and IL-1β)

while the intestinal permeability

blood diamine oxidase (DAO) level

pathological morphology of intestinal tissue and polarization of local intestinal macrophages were observed in the rats of different groups. Mouse macrophage line RAW264.7 were divided into control group

lipopolysaccharide (LPS) group and DEX group. The effect of DEX on the polarization of macrophages stimulated by LPS was determined in the cells of 3 groups.

Results

Compared with the sham group

the septic rats had significantly lower survival rate and shorter survival time (

0.01)

increased intestinal permeability and levels of pro-inflammatory cytokines (

0.01)

serious intestinal injury (including intestinal villi atrophy and rupture

obvious infiltration of red blood cells and inflammatory cells)

and enhanced iNOS expression in intestinal macrophages. Conventional treatment resulted in obviously longer survival time

but not significantly reduced intestinal permeability and pro-inflammatory cytokines

improved intestinal pathological structure

or exp

ression of iNOS when compared with the rats in the sepsis group (

0.05

0.01).

In vitro

experimental results showed that LPS stimulation induced the macrophages polarized to M1 phenotype

increased production of iNOS and TNF-α release (

0.01). DEX treatment significantly decreased iNOS expression and TNF-α level when compared with the cells of the LPS group (

0.05).

Conclusion

DEX protects the intestinal barrier function and attenuates intestinal injury in septic rats

which may be associated with its inhibition of M1 phenotype macrophage and inflammatory response.

关键词

Keywords

references

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