ADH‑503保护脂多糖引起的急性肺损伤  

ADH‑503 protects against lipopolysaccharide induced acute lung injury

作　　者：沈小康 熊锐 李东航 何如愿 刘博昊 李宁[1] 耿庆[1] SHEN Xiaokang;XIONG Rui;LI Donghang;HE Ruyuan;LIU Bohao;LI Ning;GENG Qing(Dept.of Thoracic Surgery,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院胸外科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2023年第5期528-532,537,共6页Medical Journal of Wuhan University

摘　　要：目的:研究ADH-503能否减轻脂多糖(LPS)诱导的小鼠急性肺损伤,为临床治疗急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)提供新的思路。方法:选取C57BL/6雄性野生型小鼠40只,随机分为对照组(control组)、模型组(LPS组)、ADH-503低/高剂量治疗组(LPS+ADH-503组),对照组腹腔注射生理盐水;模型组腹腔注射LPS(10 mg/kg)诱导ALI模型;ADH-503低/高用量治疗组分别腹腔注射ADH-50330 mg/kg或60 mg/kg预处理2 h后,腹腔注射LPS(10 mg/kg)。LPS灌注12 h后处死小鼠,收集小鼠肺组织,检测肺湿/干重比(W/D)值;用HE染色法观察肺组织病理损伤;ELISA检测肺组织中TNF-α、IL-1β和IL-6的含量,Western Blot检测肺组织中p-STAT3,p-NF-κB p65蛋白表达水平。结果:与对照组相比,模型组小鼠肺组织产生病理性变化,W/D比值、炎性细胞因子含量明显升高(P<0.05),急性肺损伤模型建立成功。与模型组比较,ADH-503治疗组的病理损伤评分、炎性因子水平显著降低(P<0.05),即ADH-503预处理减轻LPS诱导的小鼠急性肺损伤,且呈浓度依赖性增强。同时Western Blot的结果显示ADH-503预处理显著抑制LPS诱导的STAT3、NF-κB的磷酸化,说明ADH-503发挥作用可能通过STAT3/NF-κB信号通路。结论:ADH-503可降低由LPS所诱发小鼠肺部组织的病理变化,从而缓解肺损伤。ADH-503可以显著降低促炎性细胞因子水平,包括IL-1β、IL-6、TNF-α。ADH-503发挥抗炎作用,可能通过STAT3/NF-κB信号通路。Objective:To study whether ADH-503 can reduce lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice and provide new ideas for clinical treatment of ALI or acute respiratory distress syndrome(ARDS).Methods:Forty C57BL/6 male wild-type mice were selected and randomly divided into control group,LPS group(intraperitoneal injection of LPS),ADH-503 low/high dose treatment groups,and control group(intraperitoneally injected with normal saline).The model group were intraperitoneally injected with LPS(10 mg/kg)to induce ALI model,and the ADH-503 low/high dose treatment groups were given intraperitoneal injection of ADH-50330 mg/kg and 60 mg/kg for 2 hours,and then intraperitoneally injected with 10 mg/kg LPS.The mice were sacrificed 12 hours after LPS perfusion,and the lung tissues were collected to detect the ratio of wet/dry weight(W/D)of lung;HE staining was used to observe the pathological damage of the lung tissue;ELISA was used to detect the TNF-α,IL-1β,and IL-6 content in lung tissue.Western Blot was aodpted to detect the expression of p-STAT3 and p-NF-κB p65 proteins in lung tissue.Results:Compared with that in control group,the lung tissue in model group showed significantly pathological changes,while the wetdry weight ratio and the content of inflammatory cytokines were significantly increased(P<0.05),which means the acute lung injury models were successfully established.Compared with thaose in model group,the pathological damage scores and the levels of inflammatory factors in ADH-503 treatment group were significantly decreased(P<0.05),which means ADH-503 pretreatment attenuated LPS-induced acute lung injury in mice with a concentration-dependent enhancement.While Western Blot results showed that ADH-503 pretreatment significantly inhibited the phosphorylation of STAT3 and NF-κB expression induced by LPS,which means the anti-inflammatory effect of ADH-503 may be through the STAT3/NF-κB signaling pathway.Conclusion:ADH-503 can reduce the pathological changes in the lung of mice induced by LPS,there

关 键 词：急性肺损伤 巨噬细胞 ADH-503 

分 类 号：R655.3[医药卫生—外科学]