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

作　　者：何旋[1] 陈鹤翔 孔倩[1] 袁敏[1] 肖兴鹏[1] 吴晓静[1] He Xuan;Chen Hexiang;Kong Qian;Yuan Min;Xiao Xingpeng;Wu Xiaojing(Department of Anesthesiology,Renmin Hospital,Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院麻醉科,武汉430060

出　　处：《中华麻醉学杂志》2024年第6期729-732,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(82372156)。

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PaO_(2)并计算PaO_(2)/FiO_(2),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PaO_(2)和PaO_(2)/FiO_(2)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-κB p65表达水平升高( P<0.05);与ALI组比较,AK组大鼠PaO_(2)和PaO_(2)/FiO_(2)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-κB信号通路有关。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.

关 键 词：环己烷类 内毒素类 急性肺损伤 TOLL样受体4 NF-ΚB 

分 类 号：R965[医药卫生—药理学]