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目的 利用盐酸诱导小鼠急性肺损伤模型,研究P-选择素糖蛋白配体(PSGL-1)在其中的作用及可能机制.方法 野生型小鼠(WT)和PSGL-1敲除小鼠(PSGL-1-/-)随机分为生理盐水组和盐酸组,经导管左肺滴注生理盐水或0.1 mol/L盐酸(1μl/g体重),2h后测定小鼠肺功能指标增强呼气间歇(Penh)、PaO2和PaCO2、肺湿干重比值(W/D)以及支气管肺泡灌洗液(BALF)总蛋白浓度和白细胞计数.镜下观察靶肺组织炎症细胞浸润情况,并检测肺组织炎症因子IL-6和IL-1β及核因子-KB (NF-κB) p65、IκBa和p-IKBa蛋白表达水平.结果 盐酸刺激后,PSGL-1敲除小鼠Penh(4.77±1.22vs.5.80±0.84)和PaCO2[(63.7±3.9) mm Hgvs.(74.4±7.4) mm Hg]较WT组显著降低(P＜0.05),而PaO2较WT组显著增高[(81.0±7.1) mm Hg vs.(62.0±8.9) mm Hg,P＜0.05],肺W/D (4.86±0.15 vs.5.22±0.20)和BALF蛋白浓度[(3.71±0.64) μg/μl vs.(4.74±0.98) μg/μl]及白细胞总数[(13.00±2.18) ×107/Lvs.(49.42±3.35) ×107/L]较WT小鼠明显降低(P＜0.05).肺组织炎症因子IL-6、IL-1β及p65和p-IκBa表达水平显著低于WT组,而Iκ.Ba表达水平明显高于WT组(P＜0.05).与PSGL-1敲除小鼠比较,盐酸诱导的WT小鼠肺组织出现了更为明显的中性粒细胞和巨噬细胞浸润.生理盐水诱导的对照组小鼠各项检测指标未出现显著差异,但均明显低于其相应盐酸组(IκBa除外,P＜0.05).结论 PSGL-1可能通过激活NF-κB信号通路促进肺组织白细胞的浸润及炎症反应,在急性肺损伤疾病的发生发展中发挥重要的作用.“,”Objective To investigate the role and mechanism of P-selectin glycoprotein ligand-1 (PSGL-1) in hydrochloric acid-induced acute lung injury (ALI) in mice.Methods Wild-type mice (WT) and PSGL-1 knockout mice (PSGL-1-/-) were randomly subjected to normal saline (NS) or hydrochloric acid (HCl) challenged group.The mice were intratracheally instilled with NS or HCl (1 μl/g weight) into the left lung with a catheter.After 2 hours,respiratory function index enhanced pause (Penh),PaO2 and PaO2 were analyzed.The wet to dry weight ratio (W/D) of the left lung and total protein concentration in bronchoalveolar lavage fluid (BALF) were measured.The number of leukocytes in BALF was counted too.Targeted lung tissue was processed for further HE or immunohistochemistry staining.Meanwhile,the expressions ofinterleukin-6 (IL-6),IL-1β,nuclear factor-κB (NF-κB),IκBa and p-IκBa in lung tissue were measured.Results The Penh (4.77±1.22 vs.5.80±0.84) and PaCO2 [(63.7±3.9) mm Hg vs.(74.4±7.4) mm Hg] in the PSGL-1 knockout mice were significantly lower than those in the WT mice after HCl stimulation (P＜0.05),while the PaO2 was higher than that in the WT mice [(81.0±7.1) mm Hg vs.(62.0±8.9) mm Hg,P＜0.05)].The lung W/D ratio (4.86±0.15 vs.5.22±0.20),protein concentration [(3.71±0.64) μg/μl vs.(4.74±0.98) μg/μl] and total leukocyte count [(13.00±2.18) ×107/L vs.(49.42±3.35) ×107/L] in BALF were significantly lower in the PSGL-1 knockout mice challenged with HCl than those in the WT mice (P＜0.05).Besides,the protein expressions of IL-6,IL-1β,p65 and p-IκBa in the PSGL-1 knockout mice were lower than those in the WT mice after HC1 instillation,while the IκBa expression was higher than that in the WT mice (P＜0.05).More numbers of neutrophils and macrophages were found in the lung of the WT mice than the PSGL-1 knockout mice challenged with HCl.However,the differences of above values between the WT mice and the PSGL-1 knockout mice instilled with NS were not found,all of which were significantly lower than the correspongding HCl group except for IκBa (P＜0.05).Conclusion PSGL-l may play important roles in the development of HCl-induced ALI via the NF-κB signaling pathway and inflammation.