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
Effect of esketamine on TLR4/NF-κB signaling pathway during endotoxin-induced acute lung injury in rats
何旋 1陈鹤翔 1孔倩 1袁敏 1肖兴鹏 1吴晓静1
作者信息
- 1. 武汉大学人民医院麻醉科,武汉 430060
- 折叠
摘要
目的 评价艾司氯胺酮对大鼠内毒素性急性肺损伤时Toll样受体4(TLR4)/NF-κB信号通路的影响.方法 SPF级健康成年雄性SD大鼠30只,体质量200～220 g,8周龄,采用随机数字表法分为3组(n=10):对照组(Con组)、内毒素性急性肺损伤组(ALI组)和艾司氯胺酮组(AK组).采用腹腔注射LPS 10 mg/kg的方法制备大鼠内毒素性急性肺损伤模型.Con组腹腔注射等容量0.9％氯化钠注射液,AK组注射LPS 30 min和12 h时分别腹腔注射艾司氯胺酮10 mg/kg.模型制备后24 h时麻醉大鼠,采集颈动脉血样后处死大鼠取肺组织,测定PaO2并计算PaO2/FiO2,HE染色光镜下观察肺组织病理学结果并行肺损伤评分,电镜下观察肺组织细胞超微结构,计数支气管肺泡灌洗液(BALF)多形核白细胞(PMN),计算肺组织湿质量/干质量(W/D)比值,比色法测定髓过氧化物酶(MPO)活性,采用Western blot法检测TLR4和NF-κB p65的表达.结果 与Con组比较,ALI组大鼠PaO2和PaO2/FiO2降低,肺组织损伤评分、BALF PMN计数、肺W/D比值、MPO活性、肺组织TLR4和NF-KB p65表达水平升高(P＜0.05);与ALI组比较,AK组大鼠PaO2和PaO2/FiO2升高,肺组织损伤评分、BALF PMN计数、肺W/D比值、MPO活性、肺组织TLR4和NF-κB p65表达水平降低(P＜0.05),肺组织细胞超微结构改善.结论 艾司氯胺酮减轻大鼠内毒素性急性肺损伤的机制与阻断TLR4/NF-KB信号通路有关.
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 lipopolysac-charide 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 PaO2,and PaO2/FiO2 was calculated.The rats were then sacrificed for micro-scopic 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 leu-kocyte(PMN)in broncho-alveolar lavage fluid(BALF),activity of myeloperoxidase(MPO)(by colori-metric 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 PaO2 and PaO2/FiO2 were significantly de-creased,the lung injury score,PMN count in BALF,W/D ratio and MPO activity were increased,the ex-pression of TLR4 and NF-κB p65 was up-regulated in group ALI(P＜0.05).Compared with group ALI,PaO2 and PaO2/FiO2 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 signa-ling pathway in rats.
关键词
环己烷类/内毒素类/急性肺损伤/Toll样受体4/NF-κBKey words
Gyclohexanes/Endotoxins/Acute lung injury/Toll-like receptor 4/NF-kappa B引用本文复制引用
出版年
2024
NETL
NSTL
万方数据