布美他尼调节STING/TBK1/IRF3信号通路对急性胰腺炎大鼠炎症损伤的影响OA

Objective:To investigate effect of bumetanib on inflammatory injury in acute pancreatitis(AP)rats by regulating the stimulator of interferon gene(STING)/TANK binding kinase 1(TBK1)/interferon regulatory factor 3(IRF3)signaling pathway.Methods:Wistar rats were used to establish an AP model by combining Caerulein with lipopolysaccharide,which were grouped into an AP group,a low-dose bumetanib group,a high-dose bumetanib group and a high-dose bumetanib+DMXAA group randomly,with 10 rats in each group.Another 10 Wistar rats were included as control group.After intervention with bumetanib and STING activator DMXAA,serum amylase and lipase activities were detected in each group.HE staining was used to detect the pathological morphology of pancreatic tissue in each group.Immunohistochemical staining was applied to detect the expression of CD68 in pancreatic tissue of rats in each group and the infiltration of macrophages was evaluated based on this.ELISA was used to detect the levels of pro-inflamma-tory cytokines in each group.Western blot was used to detect the expression of pro-inflammatory cytokines and STING/TBK1/IRF3 sig-naling pathway proteins in the pancreas of rats in each group.Results:Compared with control group,the pancreatic tissue of rats in AP group showed obvious pathological damage symptoms,the serum amylase and lipase activities,pathological injury score,macrophage infiltration number,TNF-α,iNOS and IL-6 levels,TNF-α,iNOS,IL-6,STING,TBK1 and IRF3 protein expressions were obviously increased(P<0.05).Compared with AP group,the pathological damage symptoms of pancreatic tissue of rats in low and high dose bu-metanib groups were reduced,the serum amylase and lipase activities,pathological injury score,macrophage infiltration number,TNF-α,iNOS and IL-6 levels,TNF-α,iNOS,IL-6,STING,TBK1 and IRF3 protein expressions were obviously decreased(P<0.05),high-dose bumetanib had stronger effects.Compared with high-dose bumetanide group,the pathological damage symptoms of pancreatic tissue in rats in high-dose bumetanide+DMXAA group were aggravated,the serum amylase and lipase activities,patholog-ical injury score,macrophage infiltration number,TNF-α,iNOS and IL-6 levels,TNF-α,iNOS,IL-6,STING,TBK1 and IRF3 pro-tein expression were obviously increased(P<0.05).Conclusion:Bumetanib inhibits the activation of the STING/TBK1/IRF3 signaling pathway to prevent the occurrence and development of systemic and pancreatic inflammations in AP rats,thereby reducing their in-flammatory damage.