四川大学学报（医学版）2017，Vol.48Issue(4)：503-508,6.
阿魏酸钠对NALP3炎性复合体的调节及在肺纤维化中的作用
The Effect of Sodium Ferulate in Experimental Pulmonary Fibrosis via NALP3 Inflammasome
摘要
Abstract
Objective To investigate the activation of NALP3 inflammasome in the process of experimental pulmonary fibrosis (PF),and evaluate the effect of sodium ferulate (SF) in the relationship of NALP3 and PF.Methods Establishing PF experimental model via bleomycin (BLM) intratracheal injection (BLM group,SF group),treated with SF daily (SF group) or PBS [BLM group,control (CON) group] and mice were executed on day 21.Ashcroft score was used to assess lung fibrosis in mice PF model.The content of hydroxyproline (HYP) in lung tissue was determined by alkaline hydrolysis.Fibroblast NIH-3T3 was treated with H2O2 to trigger cell oxidative stress in vitro experiments (H2O2 group).Cell was pre-administrated with SF 2 h before H2O2 stimulation in H2O2 +SF group.Blank group without any treatments,was set as control.Real time-PCR was used to investigate the expressions of three elements of inflammasome [NALP3,caspase-1,apoptosis-associated specklike protein (ASC)],collagen-1 and α smooth muscle actin (a-SMA) mRNA in both lung tissue and fibroblast.Western blot was used to detect protein level of NALP3 in mice lung tissue and collagen-i,α-SMA in fibroblast as well.Meanwhile,IL-1β content in lung tissue and cell supernatant was measured by ELISA.Results In vivo experiment,SF treated mice showed lower Ashcroft score and HYP content and decreased NALP3,ASC,caspase1 mRNA expressions and IL-1β production,NALP3 protein level compared with BLM group (P＜0.05).In vitro experiment,H2O2 increased NALP3 (P＜0.05),ASC (P＜0.01),caspase-1 (P＜0.05) expressions and IL-1β releasing (P＜0.05) and promoted the expressions of collagen-1 and a-SMA in both gene and protein levels (P＜ 0.05) in NIH-3T3.NALP3 activation was partly inhibited in H2O2 + SF group (P＜ 0.05).The mRNA expression levels of collagen-1 and α-SMA were reduced in H2O2 +SF group (P＜0.05) and the protein expressions of α-SMA and collagen-1 were decreased (P＜0.05) comnpared with those of H2O2 group.Conclusion Sodium ferulate may suppress oxidative stress mediated NALP3 activation to inhibit fibroblast activation in the anti-fibrosis effect.关键词
肺纤维化/成纤维细胞/NALP3炎性复合体/阿魏酸钠Key words
Pulmonary fibrosis/Fibroblast/NALP3 infalammasome/Sodium ferulate引用本文复制引用
况菊,魏小林,谢敏..阿魏酸钠对NALP3炎性复合体的调节及在肺纤维化中的作用[J].四川大学学报（医学版）,2017,48(4):503-508,6.基金项目
四川省科技厅科技支撑计划项目(No.0040205301A53)资助 （No.0040205301A53）
