消退素D1抑制NLRP3信号通路对DSS结肠炎小鼠的影响

Resolvin D1 mitigates inflammatory response in DSS-induced colitis mice by inhibiting NLRP3 inflammasome activation

目的探讨消退素D1(resolvin D1,RvD1)对实验性结肠炎小鼠肠道炎症的影响及可能机制。方法将C57BL/6小鼠分为4组,包括正常组、RvD1对照组、葡聚糖硫酸钠(dextran sodium sulfate, DSS)模型组、RvD1治疗组。实验结束后,分离小鼠小肠及结肠组织。测量疾病活动指数(DAI),病理学评分(HI),检测髓过氧化物酶(MPO)活性水平,伊文思蓝检测肠黏膜通透性,电镜检测肠上皮细胞连接及细胞因子水平。分析NLRP3炎症小体相关基因表达水平。结果与正常组小鼠相比,模型组DAI评分、HI评分、MPO活性水平,以及结肠组织匀浆中促炎细胞因子的产生明显增加(P<0.05)。RvD1组小鼠上述实验指标明显减低(P<0.05)。模型组小鼠结肠组织NLRP3炎症小体表达水平增加(P<0.05);RvD1处理1周,小鼠结肠组织NLRP3通路相关蛋白表达水平降低(P<0.05)。结论 RvD1具有改善DSS结肠炎小鼠肠道炎症的作用,其机制可能与抑制NLRP3炎性体信号通路有关。

Aim To investigate the effect of resolvin D1(RvD1) on DSS-induced mice colitis model and the possible mechanism.Methods C57BL/6 mice were divided into four groups:normal group,control group,dextran sodium sulfate(DSS) model group,and RvD1 group.RvD1 was dissolved in physiological saline and intraperitoneally injected into experimental mice on 2nd day,4th day and 6th day.The disease activity index(DAI),histological index(HI),myeloperoxidase(MPO) were detected using Evans blue test,electron microscopy and cytokine level test.The expression differences of NLRP3,ASC,caspase-1,pro-IL-1β and other related genes were analyzed.Results The DAI score,HI score,MPO activity level,and pro-inflammatory cytokine in colon tissue homogenate were significantly raised in DSS group compared with those of the normal group( P <0.05).The above indexes of RvD1 experimental group were significantly reduced( P <0.05).At the same time,the expressions of NPRP3 pathway-related proteins,such as NLRP3,ASC,caspase-1 and pro-IL-1β,increased in DSS group( P <0.05);the expression of the above proteins decreased after RvD1 treatment( P <0.05).Conclusions RvD1 can mitigate inflammatory response in DSS-induced colitis mice,which may involve the inhibition of RvD1 of the NLRP3 inflammasome signaling pathway.