Dexmedetomidine pretreatment enhances protective effect efficacy of pericytes agaist acute lung injury in septic mice

LUO Xi; ZHANG Zisen; YANG Ao; LIU Liangming; LI Tao; HU Yi

doi:10.16016/j.2097-0927.202407011

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Dexmedetomidine pretreatment enhances protective effect efficacy of pericytes agaist acute lung injury in septic mice

Basic Medicine | 更新时间：2025-01-23

- Dexmedetomidine pretreatment enhances protective effect efficacy of pericytes agaist acute lung injury in septic mice
- Journal of Army Medical University Vol. 47, Issue 2, Pages: 101-111(2025)
- 作者机构：
  
  1.陆军特色医学中心（第三军医大学大坪医院）麻醉科，创伤与化学中毒全国重点实验室，重庆
  2.陆军特色医学中心（第三军医大学大坪医院）野战外科研究部战伤休克与输血研究室，创伤与化学中毒全国重点实验室，重庆
- 作者简介：
  
  HU Yi， E-mail： huyi921@sina. com
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(82102279)
- DOI：10.16016/j.2097-0927.202407011
  CLC： R563.9;R631;R971.93
- Published：30 January 2025，
  
  Received：02 July 2024，
  
  Revised：07 November 2024，
- 稿件说明：
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LUO XI, ZHANG ZISEN, YANG AO, et al. Dexmedetomidine pretreatment enhances protective effect efficacy of pericytes agaist acute lung injury in septic mice. [J]. Journal of army medical university, 2025, 47(2): 101-111.
DOI：

LUO XI, ZHANG ZISEN, YANG AO, et al. Dexmedetomidine pretreatment enhances protective effect efficacy of pericytes agaist acute lung injury in septic mice. [J]. Journal of army medical university, 2025, 47(2): 101-111. DOI： 10.16016/j.2097-0927.202407011.

摘要

目的

探究右美托咪定（dexmedetomidine， Dex）预处理的周细胞对脓毒症小鼠急性肺损伤（acute lung injury， ALI）的影响及其作用机制。

方法

采用腹腔内注射脂多糖（LPS） 10 mg/kg复制脓毒症小鼠模型。96只C57BL/6小鼠按照随机数字表法分为假手术（Sham）组、急性肺损伤（ALI）组、周细胞治疗（PC）组、右美托咪定（1 μmol/L）预处理后周细胞治疗（Dex-PC）组。PC组、Dex-PC组尾静脉内分别给予PC和Dex-PC（5×10

个/只），Sham组和ALI组尾静脉内给予等量生理盐水作为对照。采用流式细胞术、免疫荧光、全身体积描记系统、ELISA等方法，观察PC定植数量、肺血管通透性和肺功能的变化、血清中TNF-α和IL-6含量，以及72 h小鼠存活率和存活时间。体外使用LPS（10 μg/mL）刺激PC和Dex-PC，观察周细胞胞内ROS含量的变化。

结果

与Sham组比较，ALI组小鼠肺血管内皮细胞通透性增加，伊文思蓝大量外渗，肺组织结构严重破坏并伴随大量炎性细胞浸润，肺湿/干质量比和血清中TNF-α和IL-6表达显著升高，肺功能显著下降，且72 h无小鼠存活（

0.05）；细胞治疗后，PC组和Dex-PC组均可有效改善肺血管内皮渗漏、单位组织伊文思蓝含量、肺病理结构、肺功能以及炎症反应，明显提高存活率（

0.05），其中Dex-PC组的治疗效果明显优于PC组（

0.05）。LPS刺激PC后，ROS大量蓄积，而Dex预处理能显著抵抗LPS引起的ROS蓄积（

0.05）。

结论

右美托咪定预处理周细胞后可显著增强其对脓毒症小鼠肺血管内皮屏障功能的保护作用，其作用机制可能是其增强了周细胞抗氧化应激能力。

Abstract

Objective

‍To investigate the effect and mechanism of dexmedetomidine （Dex） pretreated pericytes （Dex-PCs） on acute lung injury （ALI） in septic mice.Methods‍　‍Mouse model of sepsis-ALI was established with intraperitoneal injection of lipopolysaccharide （LPS） at a dose of 10 mg/kg. A total of 96 C57BL/6J mice were randomly divided into sham operation （Sham） group， ALI group， PC treatment group and Dex-PCs treatment group. The mice of the PCs and Dex-PCs groups received a tail venous injection of 5×10

PC cells， respectively， whereas those of the Sham and ALI groups received equal volume of normal saline. Flow cytometry， immunofluorescence assay， whole-body volume tracing system and ELISA were used to observe the changes in the colonization of PCs， pulmonary vascular permeability， lung function， serum TNF-α and IL-6 levels， as well as the survival rate and survival time of mice at 72 h after LPS stimulation. After PCs and Dex-PCs were exposed to 10 μg/mL LPS， the level of intracellular reactive oxygen species （ROS） was measured.　‍

Results

‍Compared with the Sham group， the ALI group had increased permeability of pulmonary vascular endothelial cells， extensive extravasation of Evans blue， severely destructed of lung tissue structure and massive inflammatory cell infiltration， higher lung wet/dry weight ratio， elevated serum TNF-α and IL-6 levels， and declined lung function， and no mice survived for 72 h after modeling （

0.05）. Both PC cell treatment effectively alleviated the pulmonary vascular endothelial leakage， reduced Evans blue content per unit tissue， improved lung pathological structure， lung function and inflammatory responses， and significantly improved the survival rates in the PC group and the Dex-PC group （

0.05）. What’s more， the therapeutic effect of Dex-PC cells was significantly better than that of the PC cells （

0.05）. LPS stimulation induced ROS accumulation greatly in PCs， but no such effect was observed in the PCs after Dex pretreatment （

0.05）.　‍

Conclusion

‍Dex pretreatment significantly enhances PCs’ protective effect on pulmonary vascular endothelial barrier functions in septic mice， which may be due to its enhancing anti-oxidative capacity of PCs.

关键词

右美托咪定周细胞脓毒症急性肺损伤肺血管屏障功能

Keywords

dexmedetomidinepericytessepsisacute lung injurypulmonary vascular barrier function

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