Effect of esketamine on TLR4/NF-κB signaling pathway during endotoxin-induced acute lung injury in rats
10.3760/cma.j.cn131073.20231106.00617
- VernacularTitle:艾司氯胺酮对大鼠内毒素性急性肺损伤时TLR4/NF-κB信号通路的影响
- Author:
Xuan HE
1
;
Hexiang CHEN
;
Qian KONG
;
Min YUAN
;
Xingpeng XIAO
;
Xiaojing WU
Author Information
1. 武汉大学人民医院麻醉科，武汉 430060
- Keywords:
Gyclohexanes;
Endotoxins;
Acute lung injury;
Toll-like receptor 4;
NF-kappa B
- From:
Chinese Journal of Anesthesiology
2024;44(6):729-732
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of esketamine on Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) during endotoxin-induced acute lung injury (ALI) in rats.Methods:Thirty SPF healthy male Srague-Dawley rats, weighing 200-220 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (group Con), endotoxin-induced ALI group (group ALI) and esketamine group (group AK). Septic ALI model was developed by intraperitoneal injection of lipopolysaccharide 10 mg/kg. The equal volume of 0.9% sodium chloride was intraperitoneally injected in group Con. Esketamine 10 mg/kg was intraperitoneally injected at 30 min and 12 h after lipopolysaccharide injection in group AK. The rats were anesthetized at 24 h after developing the model, and the carotid blood samples were collected for measurement of PaO 2, and PaO 2/FiO 2 was calculated. The rats were then sacrificed for microscopic examination of the pathological changes of lung tissues which were scored and cell ultrastructure of lung tissues (with an electron microscope) and for determination of the count of the polymorphonuclear leukocyte (PMN) in broncho-alveolar lavage fluid(BALF), activity of myeloperoxidase (MPO) (by colorimetric assay) and expression of TLR4 and NF-κB p65 (by Western blot). The wet/dry lung weight (W/D) ratio was calculated. Results:Compared with group Con, the PaO 2 and PaO 2/FiO 2 were significantly decreased, the lung injury score, PMN count in BALF, W/D ratio and MPO activity were increased, the expression of TLR4 and NF-κB p65 was up-regulated in group ALI ( P<0.05). Compared with group ALI, PaO 2 and PaO 2/FiO 2 were significantly increased, the lung injury score, PMN count in BALF, W/D ratio and MPO activity were decreased, the expression of TLR4 and NF-κB p65 was down-regulated ( P<0.05), and the ultrastructure of lung tissue cells was improved in group AK. Conclusions:The mechanism by which esketamine attenuates endotoxin-induced ALI is associated with the blockade of TLR4/NF-κB signaling pathway in rats.
