Effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion in rats: an in vitro experiment
10.3760/cma.j.issn.0254-1416.2019.08.005
- VernacularTitle: 右美托咪定对大鼠肺缺血再灌注时细胞焦亡的影响:离体实验
- Author:
Xiangyan YAO
1
;
Jiaqiang ZHANG
;
Lu LI
;
Xianhui DU
;
Yanyan QI
;
Libin MA
;
Yali YANG
;
Jiangling ZHANG
;
Ning LI
;
Hui ZHANG
Author Information
1. Department of Anesthesia and Perioperative Medicine, Henan Provincial People′s Hospital, Zhengzhou 450003, China
- Publication Type:Journal Article
- Keywords:
Dexmedetomidine;
Reperfusion injury;
Lung;
Pyroptosis
- From:
Chinese Journal of Anesthesiology
2019;39(8):915-919
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion (I/R) in rats.
Methods:Adult male Sprague-Dawley rats, weighing 250-320 g, were used in this study.The model of isolated lung perfusion was established using an IL-2 Isolated Perfused Rat or Guinea Pig Lung System after the rats were anesthetized.Thirty lungs in which an ex vivo lung perfusion model was successfully established were divided into 3 groups (n=10 each) by a random number table method: control group (C group), I/R group and dexmedetomidine group (DEX group). The lungs were continuously perfused with K-H solution for 150 min in C group.After 15 min of perfusion, lungs were subjected to 60-min suspension of ventilation and perfusion, followed by 75 min of reperfusion and ventilation to establish the model of lung I/R injury in I/R and DEX groups.In DEX group, dexmedetomidine 10 nmol/L was added to K-H solution at the beginning of reperfusion.Lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope) and ultrastructure (using an electron microscope), and the alveolar damage rate (IAR) was calculated.The expression of pyroptosis-related factors including NOD-like receptor family protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β), IL-18 and gasdermin D (GSDMD) protein and mRNA was detected by Western blot or by real-time polymerase chain reaction.
Results:Compared with C group, the W/D ratio and IAR in lung tissues were significantly increased, and the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was up-regulated in I/R and DEX groups (P<0.05). Compared with I/R group, the W/D ratio and IAR in lung tissues were significantly decreased, the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was down-regulated (P<0.05), and the pathological changes were significantly attenuated in DEX group.
Conclusion:The mechanism by which dexmedetomidine reduces isolated rat lung I/R injury may be related to inhibiting pyroptosis.