Relationship between mechanism underlying methylprednisolone-induced alleviation of ventilator-induced lung injury and p38MAPK/NLRP3 pathway in lung tissues of rats
10.3760/cma.j.cn131073.20210926.01228
- VernacularTitle:甲泼尼龙减轻大鼠呼吸机相关性肺损伤机制与p38 MAPK/NLRP3通路的关系
- Author:
Zhongyan YAO
1
;
Min QU
;
Wenbo SUN
;
Ning LOU
;
Peng CHEN
;
Xiuwei SUN
;
Dongdong HUANG
Author Information
1. 沧州市中心医院麻醉科 061001
- Keywords:
Methylprednisolone;
Ventilator-induced lung injury;
NLR family, pyrin domain-containing 3 protein;
p38 Mitogen-activated protein kinases
- From:
Chinese Journal of Anesthesiology
2021;41(12):1528-1531
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the relationship between the mechanism underlying methylprednisolone-induced alleviation of ventilator-induced lung injury (VILI) and p38 mitogen-activated protein kinase (p38 MAPK)/nucleotide binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway in lung tissues of rats.Methods:Sixty clean-grade male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), mechanical ventilation group (group V), and methylprednisolone group (group M). Group C breathed air spontaneously for 4 h without mechanical ventilation.Group V was mechanically ventilated (RR 40 times/min, V T 40 ml/kg, I∶E 1∶1, PEEP 0, FiO 2 21%) for 4 h. Group M received intravenous methylprednisolone 10 mg/kg at 20 min before mechanical ventilation.At 4 h of mechanical ventilation, broncho-alveolar lavage fluid (BALF) was collected to measure the concentrations of interleukin-1beta (IL-1β), IL-18, and tumor necrosis factor-alpha (TNF-α) and wet/dry lung weight ratio (W/D ratio), and lung tissues were obtained for microscopic examination of the histopathological changes and for detection of the expression of p38MAPK, phosphorylated p38MAPK (p-p38MAPK), NLRP3, apoptosis-related speck-like protein containing a CARD (ASC), and cysteinyl aspartate-specific protease-1 (caspase-1) (using Western blot). Results:Compared with group C, the W/D ratio of lung tissues and concentrations IL-1β, IL-18 and TNF-α in BALF were significantly increased, and the expression of p-p38MAPK, NLRP3, ASC and caspase-1 was up-regulated in group V ( P<0.05), and no significant change was found in group M ( P>0.05). Compared with group V, the W/D ratio of lung tissues and concentrations of IL-1β, IL-18 and TNF-α in BALF were significantly decreased, and the expression of p-p38MAPK, NLRP3, ASC and caspase-1 was down-regulated in group M ( P<0.05). Conclusion:The mechanism by which methylprednisolone alleviates VILI may be related to inhibition of p38MAPK/NLRP3 pathway activity and reduction of inflammatory responses in lung tissues of rats.
