Resolvin D1对脂多糖诱导小鼠急性肺损伤的保护作用

Research on the protective effects of Resolvin D1 on the LPS-induced acute lung injury in mice

目的 探讨Resolvin D1（RvD1）对脂多糖（LPS）诱导小鼠急性肺损伤的治疗作用。方法体重20~25 g的BALB/c小鼠21只随机分3组,1对照组,气管内滴注PBS;2LPS模型组,气管内滴注LPS（100μg/60μl）,作用6 h;3RvD1组,在气管内滴注LPS 30 min前给予RvD1（600 ng/100μl/只）尾静脉注射,LPS作用6小时。观察各组小鼠肺组织病理组织学变化,肺泡灌洗液（BALF）中炎症细胞总数及中性粒细胞变化,BALF中促炎性细胞因子IL-6及抗炎性细胞因子IL-10含量变化及肺组织内丙二醛（MDA）的浓度。结果 在LPS刺激的小鼠中,组织病理学显示大量的炎性细胞浸润,肺泡内出血,水肿,肺组织结构明显被破坏,BALF中细胞总数、中性粒细胞及肺组织内MDA含量明显增高,BALF中促炎性细胞因子IL-6显著升高。而以RvD1预处理小鼠明显抑制LPS诱发的上述改变,同时中抗炎因子IL-10显著升高。结论 RvD1可能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。

Objective To explore the protective effects of Resolvin D1 on lipopolysaccharide （LPS）- induced acute lung injury in mice. Methods Twenty-one male BALB/c mice （20-25 g） were randomized divided into three groups. The control group was instilled with 60ul of PBS intratracheally （i. t. ）. Models of acute lung injury were administratered with 50ul of LPS （ 100 μg） （ i. t. ）. The Resolvin D1 group was treated with Resolvin D1 （RvD1） （600 ng/100 μl） orally at half hour prior to LPS challenge. After LPS administration 6 hours, histopathological changes of lung tissue and the numbers of total cells and neutrophils in bronchoalveolar lavage fluid （BALF） were observed. The levels of pro-inflammatory cytokines （IL-6） and anti- inflammatory cytokines （IL-10） in BALF and the concentration of malondialdehyde（MDA） in lung tissue were measured. Results In the LPS-induced acute lung injury mice, histopathological changes showed that the epithelial and endothelial cell structure was severely destructed, a large number of inflammatory cells infiltrated in the lung and a large mount of hemorrhage in lung tissue. Parallel with the above changes, the numbers of total cells and neutrophils, the level of IL-6 in BALF and the concentration of MDA in lung tissue increased significantly. However prior administration of RvD1 inhibited LPS induced molecular and morphological changes of acute lung injury in mice, and that this was accompanied by the elevated level of IL-10 in BALF. Conclusions RvDI rebuild the balance between pro-inflammatory response and anti-inflammatory reaction to exert protective roles in acute lung injury. Our research provide a new theoretical basis for the treatment of acute lung injury.