Therapeutic Effect And Mechanism Of Endoplasmic Reticulum Stress Inhibitor On Experimental Colitis In Mice

Introduction:The study established Inflammatory Bowel Disease(IBD)rats through Trinitro-benzene-sulfonic acid(TNBS),observing the inflammation of intestinal mucosa and detecting the expression of Grp78、CHOP 、 TGF-β and IL-17 in IBD rats via inhibiting endoplasmic reticulum stress(ERS)signaling pathway,to analyze the interaction between ERS and intestinal mucosal immunity in IBD,providing a new theoretical basis for the treatment of IBD.Method:1.Animal models of intestinal inflammation were established by TNBS,then treated with the endoplasmic reticulum stress inhibitors TUDCA or Salubrinal.Divided into four groups:solvent control group、TNBS+NS group 、TNBS+TUDCA group、TNBS+Salubrinal group.The general conditions of the mice,the length of the colon,the gross changes and the death of the mice were observed and recorded.Concurrently,the disease activity index(DAI)score was completed.2.Colonic tissues with the inflammatory lesions in eachgroup were selected for pathological sections,HE staining,histopathological score and inter-group comparison under the microscope.3.The protein expression of endoplasmic reticulum stress marker Grp78 and CHOP as well as cytokines IL-17 and TGF-β in the intestinal epithelium of each group were detected by immunohistochemical staining.Results:1.Compared with the solvent control group,grievous colitis occurred in the TNBS+NS group,which was characterized by distinctly shortened colon length,aggravated DAI score and histopathological changes.DAI and histopathological scores in the inhibitory ERS group were lower than those in the TNBS group,the parameters showed a significant difference.2.The expressions of Grp78 、 IL-17 、 TGF-β in the paracancerous colon specimens of TNBS group were bemarkedly increased,while the CHOP and were declined with compared to the solvent control group.3.ERS inhibitor(TUDCA or Salubrinal)down-regulated the expression of Grp78 、 IL-17 in the Intestinal epithelium of mice,and increased the expression of CHOP and TGF-β.Conclusions:1.Excessive ERS accelerate the formation of inflammation in IBD mice,and the degree of phlegmonosis was proportional to the expressions of Grp78,and ERS inhibition had a protective effect.2.Inhibition of ERS signaling pathway can mediate intestinal mucosal immunity by affecting the secretion of TGF-β 、IL-17.