Protection Of MicroRNA-7a-5p Antagomir Against Intestinal Mucosal Injury Related To The JNK Pathway In TNBS-induced Experimental Colitis Mouse Model

Objective: Inflammatory bowel disease(IBD)is a chronic intestinal disease with an incidence rate increasing year after year.The previous study of our group showed that microrna-7a-5p(mir-7a-5p)plays an important role in the inflammatory process of IBD,but its specific mechanism is not clear.The purpose of this study is to investigate whether mir-7a-5p regulates the inflammatory response of young mice induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS)through JNK signaling pathway,and whether mir-7a-5p antagonist has protective effect on intestinal mucosal injury,so as to provide theoretical basis for the treatment of inflammatory bowel disease.Methods: This study was divided into three groups: normal control group(NC),TNBS group and antagonist treatment group.The colitis was induced by injecting TNBS into the intestine of young male mice,and the model was established successfully.After the successful modeling of TNBS,miR-7a-5p antagonists were injected into the tail vein to become the antagonistic treatment group.The inflammatory response was evaluated by disease activity index(DAI)and histological score;the relative expression level of tight junction protein zo-1 mRNA and mir-7a-5p was detected by RT-qPCR;the protein expression level of JNK pathway protein JNK,p-JNK and tight junction protein ZO-1 was detected by Western blot.MiRNA antagonists were used to inhibit the expression of mir-7a-5p,and the injury degree of intestinal mucosa and the expression level of tight junction protein ZO-1 and JNK pathway protein were compared.Results: The expression of mir-7a-5p and phosphorylated JNK(p-JNK)in the intestinal mucosa of TNBS group was higher than that of the control group.Injection of miRNA antagonists can significantly reduce the expression of p-JNK protein,increase the expression level of ZO-1,and promote the repair of intestinal mucosal injury.Conclusion: This study confirmed that mir-7a-5p can activate JNK signal pathway to induce inflammation in TNBS induced colitis model of young mice,and mir-7a-5p antagonist can play a role of mucosal protection by inhibiting JNK phosphorylation,which provides a new research direction and theoretical basis for the treatment of IBD.