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目的 探讨重组白细胞介素-10(rIL-10)/Fc融合蛋白对内毒素诱导的急性肺损伤(ALl)小鼠炎症调控作用及其机制.方法 向气管内注射脂多糖(LPS)制成ALl动物模型;rIL-10/Fc融合蛋白采用腹腔内给药方式.132只小鼠被随机均分为正常对照组、rIL-10/Fc对照组、ALl模型组、rIL-10/Fc治疗组.每组选择25只小鼠观察24 h存活率;其余用于检测支气管肺泡灌洗液(BALF)中自细胞数量,肿瘤坏死因子-a(TNF-a)和IL-1β水平,以及肺组织髓过氧化物酶(MPO)活性、肺组织湿/干重(W/D)比值;光镜下观察肺组织病理学改变.结果 注射LPS后4 h可引起BALF中TNF-a和IL-1β显著升高(P均＜0.01),rIL-10/Fc治疗组较ALI模型组有所降低,但差异无统计学意义;但在8 h和12 h,rIL-10/Fc融合蛋白能显著抑制BALF中TNF-a产生,在12 h抑制IL-1β产生;并明显改善LPS注射24 h后实验动物的存活率(P＜0.01).rIL-10/Fc对LPS诱导的ALI小鼠BALF中白细胞数量、肺组织MPO活性、肺组织W/D比值无显著改变.注射LPS 24 h后,肺组织出现了明显的炎性改变,但在rlL-10/Fc融合蛋白干预后没有出现显著的差异.结论 rIL-10/Fc融合蛋白能显著抑制LPS诱导的ALI小鼠肺促炎细胞因子产生,改善预后.“,”Objective To clarify the regulatory role and mechanism of recombinant interleukin-10/Fc (rIL-10/Fc)fusion protein on inflammatory parameters during development of acute lung injury(ALI)induced by lipopoIysaccharide(LPS)in a murine model.Methods An ALI model was reproduced by intra-tracheal injection of LPS.rlL-10/Fc was administered intraperitonealy.One hundred and thirty-two BALB/c mice were divided into four groups,including saline control group,rlL-10/Fc control group,ALI model group,and rIL-10/Fc treatment group.Twenty-four-hour survival rate was determined in 25 mice of each group.The number of inflammatory cells and inflammatory mediators in bronchia-alveolar lavage fluid (BALF),tumor necrosis factor-a(TNF-a)and IL-1β,and also lung myeloperoxidase(MPO)activity,lung wet/dry(W/D)ratio were determined in the rest of mice.Pathological changes in lung were examined with hematoxylin-eosin(HE)staining,and inflammatory change was evaluated under microscope.Results Levels of TNF-a and IL-1β in BALF were substantially increased 4 hours after intra-tracheal LPS(both P＜0.01),and they were lowered but without significant difference after rIL-10/Fc administration.However,rlL-10/Fc fusion protein markedly attenuated release of TNF-a at 8 hours and 12 hours,and IL-1β was lowered at 12 hours after LPS challenge.Pre-treatment with rlL-10/Fc fusion protein significantly improved survival rate at 24 hours in LPS challenged mice(P＜0.01).There was no significant difference in cell count in BALF,MPO,lung W/D ratio,after treatment of rlL-10/Fc fusion protein.Obvious inflammatory changes were found in lung was found pathologically at 24 hours after LPS injection,but there was no significant difference compared with ALI mice with rIL-10/Fc fusion protein administration.Conclusion rIL-10/Fc fusion protein inhibits release of TNF-a and IL-1β in BALF in a LPS-induced ALI murine model.rIL-10/Fc fusion protein improves survival rate in ALI mice by decreasing the release of pro-inflammatory cytokines.