DHA对小鼠急性肺损伤的保护作用及可能的机制研究

目的 探讨二十二碳六烯酸（docosahexaenoic acid,DHA）对LPS诱导小鼠急性肺损伤的治疗作用及可能的机制.方法 体重20-25 g的BALB/c小鼠18只随机分为3组：①对照组,气管内滴注PBS;②LPS模型组,气管内滴注LPS （100μg/50 μl）,作用6h;③DHA组,连续给予DHA（500 mg/kg）灌胃连续预处理7d,再气管内滴注LPS（100 μg/50μl）作用6h.观察各组小鼠肺组织病理组织学变化,肺泡灌洗液（BALF）中白细胞总数及髓过氧化物酶活性变化,以及BALF中促炎性细胞因子IL-1β、IL-6及抗炎性细胞因子IL-10含量变化. 结果 与对照组比较,LPS模型组小鼠的组织病理学显示明显的肺泡壁结构破坏,炎性细胞浸润增多及肺组织出血加重,BALF中的白细胞总数及肺组织内髓过氧化物酶活性明显增高,BALF中促炎性细胞因子IL-1β、IL-6显著升高（P＜0.01）,保护性细胞因子IL-10较对照组有所升高,但差异没有统计学意义（P＞0.05）.与LPS模型组比较,DHA预处理组小鼠的肺泡壁结构破坏受到抑制,炎性细胞浸润及组织出血减少,BALF中IL-1β、IL-6浓度显著下降（P＜0.01）,同时BALF中抗炎因子IL-10显著升高（P＜0.01）. 结论 DHA通过重建抗炎反应和炎症反应的平衡对急性肺损伤发挥保护作用.

Research on the protective effect and possible mechanism of DHA on acute lung injury in mice

Objective To investigate the protective effect and possible mechanism of DHA on lipopolysaccharide（LPS）-induced acute lung injury in mice.Methods Eighteen male BALB/c mice （20-25 g） were randomized into three groups.The mice in control group were intratracheally instilled with 50 μl of sterile PBS.The mice in LPS model group were instilled intratracheally with LPS （100μg/50 μl） for 6 h.The mice in DHA group were orally administered with docosahexaenoic acid（DHA） （500 mg/kg） for 7 consecutive days,then LPS （100 μg/50 μl） instilled intratracheally for 6 h.Histopathological changes of lung tissue,the numbers of total white blood cells in bronchoalveolar lavage fluid（BALF） and the activity of myeloperoxidase（MPO） in lung tissue in each group were observed.The levels of pro-inflammatory cytokines（IL-1β,IL-6） and anti-inflammatory cytokines（IL-10） in BALF were measured by ELISA.Results Compared with control group,the destruction of alveolar wall structure of mice in LPS model group were more obvious.Compared with control group,the infiltration of inflammatory cells were increased and hemorrhage was aggravated in LPS model group.As compared with control group,the total number of white blood cells in BALF and myeloperoxidase activity in lung tissue were increased in LPS model group.Compared with control group,proinflammatory cytokines IL-1 β,IL-6 were significantly increased in BALF in LPS model group（P ＜0.01）and protective cytokine IL-10 was increased,but there was no significant difference（P ＞ 0.05）.Compared with LPS model group,DHA pretreatment inhibited the damage of alveolar wall structure in mice,inflammatory cell infiltration and tissue hemorrhage induced by LPS.The concentrations of IL-1β,IL-6 in BALF decreased significantly in DHA group（P ＜ 0.01）,while antiinflammatory factor IL-10 increased significantly in BALF as compared with DHA group（P ＜ 0.01）.Conclusion DHA has protective effects on acute lung injury by rebuilding the balance between