基于NF-κB信号通路探讨酸浆内酯B对溃疡性结肠炎的抗炎作用

Investigation on the anti-inflammatory effect of physapubescin B on ulcerative colitis based on NF-κB signaling pathway

目的:探究酸浆内酯B(PB)在溃疡性结肠炎(UC)中发挥的抗炎作用。方法:建立LPS诱导的斑马鱼炎症模型,分为对照组、模型组、吲哚美辛组、PB组,观察各组斑马鱼肠道中的中性粒细胞数量;DSS诱导的小鼠UC模型,分为对照组、模型组、美沙拉嗪组、PB组,连续监测各组小鼠体质量、粪便性状及隐血情况,比较肠道黏膜的病理改变及相关炎症因子的表达;LPS诱导的细胞炎症模型,分为对照组、LPS组、PB组,观察各组相关炎症因子蛋白表达水平。结果:斑马鱼模型:PB组斑马鱼中性粒细胞数量较模型组显著减少(P<0.01)。小鼠模型:PB组小鼠体质量、疾病活动度评分、结肠长度较模型组显著改善(P<0.01);炎症因子TNF-α、IL-1β及IL-6在蛋白水平上显著降低(P<0.01)。细胞模型:PB组相关炎症因子TNF-α、IL-1β表达较LPS组显著降低(P<0.05,P<0.01),NF-κB相关信号通路的蛋白表达水平也得到了抑制。结论:对于UC,PB可以发挥抗炎作用,与下调NF-κB信号通路、降低炎症因子的表达和中性粒细胞的水平有关。

Objective:To explore the anti-inflammatory effect of physapubescin B in ulcerative colitis.Methods:Established LPS induced zebrafish inflammatory model,divided into control group,model group,indomethacin group and PB group.Observed the number of neutrophils in the intestine of zebrafish in each group.Mouse model of ulcerative colitis induced by DSS,divided into control group,model group,mesalazine group and PB group.The weight,fecal characteristics and occult blood were monitored continuously in each group,the pathological changes of intestinal mucosa and the expression of related inflammatory factors were compared.LPS induced cell inflammatory model,divided into control group,LPS group and PB group.Observe the protein expression levels of related inflammatory factors in each group.Results:Zebrafish model:The number of neutrophils of zebrafish in PB group was significantly reduced compared with model group(P<0.01).Mouse model:The weight,disease activity score and colon length of mice in PB group were significantly improved(P<0.01);the levels of inflammatory cytokines TNF-α,IL-1βand IL-6 decreased significantly(P<0.01).Cell model:The expressions of TNF-αand IL-1βin PB group were significantly lower than those in LPS group(P<0.05,P<0.01),the protein expression level of NF-κB related signaling pathway was also inhibited.Conclusion:PB can play an anti-inflammatory effect on ulcerative colitis by down-regulating NF-κB signaling pathway,and reducing the expression of inflammatory factors and the level of neutrophils.