消退素D1对急性肺损伤小鼠肺部炎症反应和Nod样受体蛋白3表达的影响

Influence of Resolvin D1 on the inflammatory response and expression of NLRP3 in mice with acute lung injury

目的观察消退素D1(RvD1)对急性肺损伤小鼠肺部炎症反应和Nod样受体蛋白3(NLRP3)炎性小体表达的影响。方法体质量25~30 g的BALB/c小鼠30只分为3组(各10只),正常对照组鼠尾静脉注射等体积9 g/L盐水;脂多糖(LPS)组小鼠尾静脉注射LPS(10 mg/kg),作用6 h;RvD1组小鼠注射LPS 30 min前予RvD1(5μg/kg)尾静脉注射,LPS作用6 h。观察各组小鼠肺组织病理学改变,肺部炎性因子白细胞介素-18(IL-18)、白细胞介素-1β(IL-1β)及NLRP3炎性小体的表达改变。结果LPS组小鼠经LPS刺激后,小鼠肺组织出现病理损伤,炎性因子IL-18、IL-1β水平均较正常对照组小鼠明显升高,差异均有统计学意义(均P<0.05),肺组织NLRP3、凋亡相关点样蛋白(ASC)及半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)表达较正常对照组小鼠明显升高,差异均有统计学意义(均P<0.05)。RvD1组小鼠予RvD1预处理后,肺组织病理损伤减轻,炎性因子IL-18、IL-1β水平较LPS组均明显降低,差异均有统计学意义(均P<0.05);同时RvD1组NLRP3、ASC及Caspase-1表达较LPS组显著降低,差异均有统计学意义(均P<0.05)。结论RvD1能减轻急性肺损伤肺部炎症反应,抑制炎性因子的释放,该效应与抑制NLRP3的表达有关。

Objective To investigate the effects of Resolvin D1(RvD1)on the inflammatory response and the expression of Nod-like receptor protein 3(NLRP3)inflammasomes in mice with acute lung injury.Methods The 30 male BALB/c mice weighing 25-30 g were divided into 3 groups(each group with 10 mice).Mice in the normal control group were given normal saline by tail vein injection.Mice in the lipopolysaccharide(LPS)group were given the same volume of LPS(10 mg/kg)via tail vein injection.Mice in the RvD1 group were injected with RvD1(5μg/kg)through the tail vein 30 minutes prior to LPS administration.Mice were humanely sacrificed after 6 hours.Histopatholo-gical changes of lung tissue,the levels of pro-inflammatory cytokines interleukin(IL)-18 and IL-1β,and the expression of NLRP3 inflammasomes in lung tissue were measured.Results After LPS administration,the lung of mice showed pathological damage.The levels of pro-inflammatory factors IL-18 and IL-1βas well as the expression of NLRP3,apoptosis-associated speck-like protein containing a card(ASC)and Caspase-1 in the LPS group were significantly higher than those in the normal control group(all P<0.05).After pretreatment with RvD1,the pathological damage of lung tissue was alleviated.The levels of pro-inflammatory factors IL-18 and IL-1β as well as the expression of NLRP3,ASC and Caspase-1 in the RvD1 group were significantly lower than those in the LPS group(all P<0.05).Conclusions RvD1 can attenuate the pulmonary inflammation in acute lung injury and inhibit the release of pro-inflammatory factors,which is possibly related to the suppression of NLRP3.