西维来司他钠对小鼠内毒素性急性肺损伤时SPMs合成酶表达的影响  

Effect of sodium sivelestat on expression of SPMs synthesis enzymes in mice with lipopolysaccharide-induced acute lung injury

作　　者：刘川宁 史佳[1] 李雨杭 朴美玲 刘华洋 李秋佳 余剑波[1] Liu Chuanning;Shi Jia;Li Yuhang;Piao Meiling;Liu Huayang;Li Qiujia;Yu Jianbo(Department of Anesthesiology and Critical Care Medicine,Tianjn Nankai Hospital,Tianjin Medical University,Tianjin 300100,China)

机构地区：[1]天津医科大学附属南开医院麻醉与重症医学科,天津300100

出　　处：《中华麻醉学杂志》2024年第11期1386-1390,共5页Chinese Journal of Anesthesiology

基　　金：天津市科技计划项目多元投入基金项目面上项目(21JCYBJC01240)。

摘　　要：目的评价西维来司他钠对小鼠内毒素性急性肺损伤(ALI)时特异性促炎症消退介质(SPMs)合成酶表达的影响。方法SPF级健康野生型雄性C57BL/6小鼠18只,6~8周龄,体质量20~25 g。采用随机数字表法将小鼠分为3组(n=6):对照组(C组)、内毒素性ALI组(ALI组)和内毒素性ALI+西维来司他钠组(ALI+SV组)。采用尾静脉注射LPS 15 mg/kg的方法制备大鼠内毒素性ALI模型。SV组于给予LPS后1 h腹腔注射西维来司他钠50 mg/kg。给予LPS后12 h时取小鼠眼球血测血常规,剩余血液提取血清,随后麻醉小鼠处死取肺组织,确定湿/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ELISA法测定血清IL-1β和IL-10浓度;采用Western blot法检测肺组织中性粒细胞弹性蛋白酶(NE)及SPMs合成酶[5-脂氧合酶(5-LOX)、12-脂氧合酶(12-LOX)、15-脂氧合酶(15-LOX)]的表达。结果与C组比较,ALI组肺损伤评分、W/D比值、白细胞计数、中性粒细胞百分比、血清IL-1β和IL-10浓度升高,NE表达上调,肺组织5-LOX、12-LOX和15-LOX表达下调(P<0.05);与ALI组比较,ALI+SV组肺损伤评分、W/D比值、白细胞计数、中性粒细胞百分比、血清IL-1β浓度降低,IL-10浓度升高,NE表达下调,肺组织5-LOX、12-LOX和15-LOX表达上调(P<0.05)。结论西维来司他钠减轻小鼠内毒素性ALI的机制可能与上调SPMs合成酶表达,促进肺内炎症消退有关。Objective To evaluate the effect of sodium sivelestat on the expression of specialized pro-resolving mediators(SPMs)synthesis enzymes in mice with lipopolysaccharide(LPS)-induced acute lung injury(ALI).Methods Eighteen SPF healthy male C57BL/6 mice,aged 6-8 weeks,weighing 20-25 g,were divided into 3 groups(n=6 each)using a random number table method:control group(C group),LPS-induced ALI group(ALI group),and LPS-induced ALI+sodium sivelestat group(ALI+SV group).ALI was induced by intravenous injection of LPS 15 mg/kg through the tail vein.Sodium sivelestat 50 mg/kg was intraperitoneally injected at 1 h after LPS administration.At 12 h after LPS administration,blood samples were collected from the eyeballs for routine blood tests,and the remaining blood was processed for serum extraction.The mice were sacrificed after anesthesia,and lung tissues were collected to determine the wet/dry weight(W/D)ratio,serum concentrations of interleukin-1beta(IL-1β)and IL-10(by enzyme-linked immunosorbent assay),expression of neutrophil elastase(NE)and SPMs synthesis enzymes 5-lipoxygenase(5-LOX),12-lipoxygenase(12-LOX),and 15-lipoxygenase(15-LOX)in lung tissues(by Western blot)and to examine the pathological changes of lung tissues which were scored.Results Compared with C group,the lung injury scores,W/D ratio,white blood cell counts,percentage of neutrophil,and serum IL-1β and IL-10 concentrations were significantly increased,the expression of NE was up-regulated,and the expression of 5-LOX,12-LOX and 15-LOX was down-regulated in ALI group(P<0.05).Compared with ALI group,the lung injury scores,W/D ratio,white blood cell counts,percentage of neutrophil,and serum IL-1β concentration were significantly decreased,the serum IL-10 concentration was increased,the expression of NE was down-regulated,and the expression of 5-LOX,12-LOX and 15-LOX was up-regulated in ALI+SV group(P<0.05).Conclusions The mechanism by which sodium sivelestat alleviates LPS-induced ALI may be related to up-regulating the expression of SPMs synthesis enzym

关 键 词：蛋白酶抑制蛋白质类 分泌 内毒素类 急性肺损伤 炎症 

分 类 号：R614[医药卫生—麻醉学]