紫菀酮基于ERK/NLRP3/IL-1β信号通路对溃疡性结肠炎大鼠的作用及其机制研究OA

Objective To explore the effects and mechanism of shionone on ulcerative colitis in rats based on the extracellular regulated protein kinase(ERK)/NOD-like receptor protein 3(NLRP3)/interleukin(IL)-1β signaling pathway.Methods A total of 60 rats were randomly divided into normal group,model group,experimental-L group,experimental-H group and activator group by random number table method,with 12 rats in each group.The normal group was given drinking water without dextran sulfate sodium,while the other groups were fed with drinking water containing 5％dextran sulfate sodium for 10 days to establish ulcerative colitis rat models.After modeling,rats were administered for 7 days.The experimental-L and-H groups were intragastrically given 50 and 100 mg·kg-1 shionone daily,respectively;the activator group was intragastrically given 100 mg·kg-1 shionone daily combined with intraperitoneal injection of 4 mg·kg-1 ERK activator RO 67-7476;the normal group and model group were intragastrically given and intraperitoneally injected with equal volumes of normal saline daily.Disease activity index was analyzed;the levels of IL-17 and IL-23 in colon tissue were detected by enzyme-linked immunosorbent assay(ELISA);colonic histopathological changes were observed by hematoxylin-eosin(HE)staining;intestinal mucosa was detected by Alcian blue-periodic acid-Schiff(AB-PAS)staining;the relative expression levels of phosphorylated(p)-ERK,NLRP3 and IL-1 β proteins were determined by Western blot.Results Rats in the model group showed severe colonic tissue damage,characterized by disappearance of intestinal mucosa,blurred epithelial cell structure,gland atrophy,inflammatory cell infiltration,lamellar necrosis of the colonic mucosal layer and decreased number of goblet cells.The disease activity index scores in the normal group,model group,experimental-L group,experimental-H group and activator group were(0.12±0.02),(2.98±0.34),(1.76±0.19),(0.55±0.07)and(2.69±0.29)points,respectively;the levels of IL-17 in colon tissue were(24.64±2.74),(39.78±4.27),(32.92±3.65),(26.13±2.85)and(37.85±3.98)pg·mL-1,respectively;the levels of IL-23 in colon tissue were(14.25±1.73),(28.47±3.04),(22.14±2.42),(15.96±1.87)and(26.95±2.94)pg·mL-1,respectively;the histopathological scores of colon tissue were(0±0),(3.73±0.39),(2.49±0.28),(1.24±0.15)and(3.61±0.38)points,respectively;the p-ERK/ERK in colon tissue were 0.32±0.04,0.81±0.09,0.58±0.07,0.36±0.05 and 0.77±0.08,respectively;the relative expression levels of NLRP3 protein were 1.03±0.11,2.05±0.23,1.64±0.18,1.24±0.14 and 1.95±0.22,respectively;the relative expression levels of IL-1 β protein were 1.05±0.11,1.96±0.22,1.58±0.17,1.21±0.13 and 1.91±0.21,respectively.Statistical significance was observed in the above indicators when comparing the normal group with the model group,comparing the model group with the experimental-L,H groups and comparing the experimental-H group with the activator group(all P＜0.05).Conclusion Shionone has protective effects on rats with ulcerative colitis by inhibiting the ERK/NLRP3/IL-1 β signaling pathway.