当归多糖调节NLRP3/IL-1β信号通路对脓毒症大鼠肠黏膜损伤和免疫功能的影响OA

Objective:To evaluate effects of Angelica sinensis polysaccharide(ASP)on intestinal mucosal injury and immune function in septic rats and to preliminarily investigate potential mechanisms.Methods:A rat model of concentrative sepsis was pre-pared by cecum ligation and puncture(CLP)method.Rats were divided into Sham group,CLP group,low-dose ASP group(L-ASP group),medium-dose ASP group(M-ASP group),high-dose ASP group(H-ASP group),ASP+Nigericin group(ASP+N group)and Nigericin group(ASP+N group)according to randomized number table method,with 21 rats in each group.L-ASP,M-ASP and H-ASP groups were given 100,200 and 400 mg/kg ASP by gavage,respectively.ASP+N group was given 1 mg/kg NLRP3 activator Nigericin intraperitoneally on top of 400 mg/kg ASP by gavage.Equal doses of saline were given by gavage in Sham and CLP groups.Intestinal mucosal injury was assessed using HE staining and Chiu's score.Intestinal epithelial barrier function was assessed using diamine oxidase(DAO)activity assay and urinary lactose/mannitol(L/M)ratio.Serum and ileal tissue levels of IL-6,IL-1β and IL-10 were detected by ELISA.Peripheral blood T-lymphocyte subsets were detected by flow cytometry.Western blot was used to analyze intestinal epithelial barrier and NLRP3 inflammatory vesicle-associated protein expression.Results:Intestinal mucosa of CLP rats showed pathological damage such as inflammatory cell infiltration,irregular arrangement of intestinal villi,and enlarged villus gap,intestinal mucosal Chiu's score,serum DAO and urinary L/M were increased,expressions of Claudin-3,ZO-1 and occludin pro-teins were decreased in tissue of ileal mucosa,IL-6 and IL-1β levels were significantly increased,while IL-10 level was significantly decreased in serum and ileal mucosal tissues,proportion of CD4+T cells and CD4+T/CD8+T in peripheral blood were significantly de-creased.ASP treatment was able to reduce intestinal mucosal tissue damage,improve barrier function,and reduce body and intestinal immune-inflammatory responses in septic rats,reduced expressions of NLRP3,ASC and cleaved caspase-1 in intestinal tissues of sep-tic rats;while NLRP3 activator Nigericin could attenuate modulating effect of angelica polysaccharides on intestinal mucosal injury and immune-inflammatory response to some extent.Conclusion:ASP ameliorates intestinal mucosal injury,protects intestinal epithelial barrier integrity,and reduces organismal and intestinal immune-inflammatory responses in septic rats,which may be achieved through inhibition of NLRP3/IL-1β pathway activation.