脂氧素A4对内毒素诱导小鼠肺内炎症反应的影响

Protective effect of lipoxin A4 on lipopolysaccharide-induced pulmonary inflammatory response in mice

目的探讨脂氧素A4对脂多糖诱导小鼠急性肺内炎症反应的影响。方法36只雄性C57BL/6小鼠,随机分为对照组、脂氧素A4组、ZnPP组、内毒素组、脂氧素A4治疗组和ZnPP+脂氧素A4治疗组,每组6只。雾化吸入脂多糖8 h后,测定肺泡灌洗液总蛋白浓度和TNF-α含量,测定肺组织湿干质量比值、丙二醛(MDA)活性和一氧化氮(NO)浓度,免疫组化测定肺组织HO-1的蛋白表达。结果与LPS组比较,脂氧素A4治疗组肺水肿减轻,肺泡灌洗液总蛋白浓度、TNF-α含量、肺组织MDA活性、NO含量均降低(P<0.01),而HO-1的蛋白表达明显升高,肺组织损伤减轻。HO-1抑制剂ZnPP减弱脂氧素A4保护作用。结论脂氧素A4能减轻内毒素诱导的肺部急性炎症反应,HO-1介导其保护作用。

Objective To investigate whether lipoxin A4 could attenuate lipopolysaccharide induced pulmonary inflammatory response in mice. Methods All of the animals were randomly assigned to one of six groups （ n = 6 per group） and were＇given either LPS （0.3 mg/ml） or saline, post- treated with lipoxin A4 （0.1 mg/kg intravenously） or vehicle （10% ethanol） 60 min after LPS inhalation; The heme oxygenase - 1 （ HO - 1 ） inhibitor Zinc protoporphyrin IX （ ZnPP, 25 mg/kg intravenously） or its vehicle （0.9% saline） was given 30 rain before lipoxin A4 injection. Results Inhalation of LPS increased total protein concentration, TNT - α concentration in BALF and also increased wet to dry weight （ W/D） ratio, MDA and NO in lung tissue. Post -treatment with lipoxin A4 inhibited TNF - α, nitric oxide and malondialdehyde production, with the outcome of decreased pulmonary edema, lipid peroxidation in lung tissue. In addition, immunohistochemical analysis revealed that lipoxin A4 promoted the formation of HO - 1 in the lung tissue. The beneficial effects of lipoxin A4 were abolished by the ZnPP. Conclusion Lipoxin A4 significantly reduces LPS - induced pulmonary inflammatory response in mice; HO -1 plays an essential role in the anti -inflammatory and pro- resolution bioactions of lipoxin A4.