西格列汀对小鼠内毒素性肺损伤时黏蛋白5AC表达的影响  

Effect of sitagliptin on expression of airway mucin 5AC in mice with endotoxin-induced lung injury

作　　者：王佳佳[1] 魏苗苗 秦伟伟[1] 张晓[1] 马福国[1] 孙立新[1] 韩伟[2] Wang Jiajia;Wei Miaomiao;Qin Weiwei;Zhang Xiao;Ma Fuguo;Sun Lixin;Han Wei(Department of Anesthesiology,Qingdao Municipal Hospital,Medical College of Qingdao University,Qingdao 266071,China;Department of Respiratory and Critical Care Medicine,Qingdao Municipal Hospital,Medical College of Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学附属青岛市市立医院麻醉科,青岛266071 [2]青岛大学附属青岛市市立医院呼吸与危重症科,青岛266071

出　　处：《中华麻醉学杂志》2023年第9期1124-1128,共5页Chinese Journal of Anesthesiology

摘　　要：目的评价西格列汀对小鼠内毒素性肺损伤时黏蛋白5AC(MUC5AC)表达的影响。方法SPF级健康雄性C57BL/6小鼠36只,6~8周龄,体质量20~25 g,按照随机数字表法分为3组(n=12):对照组(C组)、内毒素性肺损伤组(L组)和内毒素性肺损伤+西格列汀组(S组)。L组和S组气管内滴注LPS 3 mg/kg制备小鼠内毒素性肺损伤模型,C组小鼠气管内滴注等量生理盐水。S组于LPS滴注前1 h腹腔注射西格列汀100 mg/kg,C组和L组小鼠于气管内滴注生理盐水前1 h腹腔注射生理盐水。LPS或生理盐水滴注后24 h时经股动脉采血行动脉血气分析测定PaO_(2)及葡萄糖水平,随后处死小鼠收集支气管肺泡灌洗液(BALF)和肺组织,ELISA法检测血清及BALF IL-6、IL-1β和TNF-α浓度。称重后计算肺组织湿质量/干质量(W/D)比值,HE染色法观察肺组织病理学结果并行肺损伤评分,采用免疫组化法及免疫组化综合评分法检测MUC5AC的表达,采用qRT-PCR法检测肺组织MUC5AC的mRNA表达水平。结果与C组比较,L组和S组PaO_(2)降低,葡萄糖水平、W/D比值和肺损伤评分升高,血清及BALF IL-6、IL-1β和TNF-α浓度升高,肺组织MUC5AC及其mRNA表达上调(P<0.05);与L组比较,S组PaO_(2)升高,葡萄糖水平、W/D比值、肺损伤评分降低,血清及BALF IL-6、IL-1β和TNF-α浓度降低,肺组织MUC5AC及其mRNA表达下调(P<0.05)。结论西格列汀减轻小鼠内毒素性肺损伤与下调MUC5AC表达有关。Objective To evaluate the effect of sitagliptin on the expression of airway mucin 5AC(MUC5AC)in mice with endotoxin-induced lung injury.Methods Thirty-six healthy male SPF C57BL/6 mice,aged 6-8 weeks,weighing 20-25 g,were divided into 3 groups(n=12 each)using a random number table method:control group(group C),endotoxin-induced lung injury group(group L),and endotoxin-induced lung injury+sitagliptin group(group S).Lipopolysaccharide(LPS)3 mg/kg was intratracheally infused to prepare endotoxin-induced lung injury model in L and S groups,while the equal volume of normal saline was given instead in group C.Sitagliptin 100 mg/kg was intraperitoneally injected at 1 h before LPS infusion in group S,and normal saline was intraperitoneally injected at 1 h before endotracheal infusion in C and L groups.The arterial blood samples from femoral artery were taken at 24 h of LPS or normal saline infusion for measurement of PaO_(2) and glucose levels.The mice were then sacrificed,and broncho-alveolar lavage fluid(BALF)and lung tissues were collected for determination of the concentrations of interleukin-6(IL-6),interleukin-1beta(IL-1β),and tumor necrosis factor-alpha(TNF-α)in serum and BALF(by enzyme-linked immunosorbent assay),wet/dry weight ratio(W/D ratio),expression of MUC5AC(by immunohistochemistry and immunohistochemical comprehensive score),and expression of MUC5AC mRNA in lung tissues(by quantitative real-time polymerase chain reaction)and for examination of the pathological changes of lung tissues(using haematoxylin and eosin staining)which were scored.Results Compared with group C,PaO_(2) was significantly decreased,the glucose levels,W/D ratio and lung injury score were increased,the concentrations of IL-6,IL-1βand TNF-αin serum and BALF were increased,and the expression of MUC5AC mRNA in lung tissues was up-regulated in L and S groups(P<0.05).Compared with group L,PaO_(2) was significantly increased,the glucose levels,W/D ratio and lung injury score were decreased,the concentrations of IL-6,IL-1βand TNF-αin se

关 键 词：二肽基肽酶Ⅳ抑制剂 内毒素类 急性肺损伤 黏蛋白5AC 

分 类 号：R965[医药卫生—药理学]