摘要
目的评价艾司氯胺酮对内毒素性急性肺损伤大鼠肺组织细胞焦亡的影响。方法SPF级健康成年雄性SD大鼠30只,体重200~220 g,8周龄。采用随机数字表法分为3组(n=10):对照组(C组)、内毒素性急性肺损伤组(ALI组)和艾司氯胺酮组(E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。C组腹腔注射等容量0.9%氯化钠注射液;E组注射LPS 30 min时腹腔注射艾司氯胺酮10 mg/kg。于注射LPS后24 h时心脏采血后处死取肺组织,采用ELISA法检测血清IL-1β和IL-18的浓度,确定肺组织湿重/干重(W/D)比值,采用比色法测定髓过氧化物酶(MPO)活性,采用Western blot法检测肺组织NOD样受体热蛋白结构域相关蛋白3(NLRP3)、caspase-1和消皮素D(GSDMD)的表达,HE染色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。结果与C组比较,ALI组和E组大鼠肺损伤评分、肺组织W/D比值、MPO活性、NLRP3、caspase-1、GSDMD表达水平、血清IL-1β和IL-18浓度升高(P<0.05);与ALI组比较,E组大鼠肺损伤评分、肺组织W/D比值、MPO活性、NLRP3、caspase-1、GSDMD表达水平、血清IL-1β和IL-18浓度降低(P<0.05)。结论艾司氯胺酮减轻大鼠内毒素性急性肺损伤的机制与抑制肺组织细胞焦亡有关。
Objective To evaluate the effects of esketamine on pyrolysis in lung tissues of rats with endotoxin-induced acute lung injury(ALI).Methods SPF healthy adult male Sprague-Dawley rats,weighing 200-220 g,aged 8 weeks,were divided into 3 groups(n=10 each)using a random number table method:control group(group C),endotoxin-induced ALI group(group ALI)and esketamine group(group E).Lipopolysaccharide(LPS)10 mg/kg was intraperitoneally injected to establish the model of endotoxin-induced ALI model.The equal volume of 0.9%sodium chloride injection was intraperitoneally injected in group C.Esketamine 10 mg/kg was intraperitoneally injected at 30 min of injection of LPS in group E.Lung tissues were removed after blood samples were collected from hearts at 24 h after injection of LPS for determination of concentrations of serum interleukin-1beta(IL-1β)and IL-8(by enzyme-linked immunosorbent assay),the wet/dry weight ratio(W/D ratio),activities of myeloperoxidase(MPO)(by colorimetric assay)and the expression of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3(NLRP3),caspase-1 and gasdermin D(GSDMD)(by Western blot)and for examination of pathological changes which were scored after haematoxylin and eosin staining and ultrastructure(using an electron microscope).Results Compared with group C,the lung injury score,W/D ratio,MPO activity,expression of NLRP3,caspase-1 and GSDMD and concentrations of IL-1βand IL-18 in serum were significantly increased in ALI and E groups(P<0.05).Compared with group ALI,the lung injury score,W/D ratio,MPO activity,expression of NLRP3,caspase-1 and GSDMD and concentrations of IL-1βand IL-18 in serum were significantly decreased in group E(P<0.05).Conclusion The mechanism by which esketamine reduces endotoxin-induced ALI is related with inhibition of pyrolysis in lung tissues of rats.
作者
何旋
吴晓静
陈鹤翔
孔倩
袁敏
明婷倩
夏中元
He Xuan;Wu Xiaojing;Chen Hexiang;Kong Qian;Yuan Min;Ming Tingqian;Xia Zhongyuan(Department of Anesthesiology,Renmin Hospital,Wuhan University,Wuhan 430060,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2021年第3期331-334,共4页
Chinese Journal of Anesthesiology
基金
国家自然科学基金(81970722,81901952)
湖北省自然科学基金(2019CFB473)。
