Study On The Protective Effect Of Dexmedetomidine On Intestinal Mucosal Barrier Damage In Septic Rats Through Wnt/β-catenin Signaling Pathway And Tight Junction Protein

Objective:To explore the mechanism of dexmedetomidine’s protective effect on intestinal mucosal injury in SD rats with sepsis through Wnt/β-catenin signaling pathway and tight junction protein,which can be used for the treatment of intestinal sepsis and organ protection in clinical practice.Provide a theoretical basis.Methods:Sixty SD male rats of appropriate age were selected and randomly divided into three groups(control group,sepsis group and dexmedetomidine group,20 rats in each group).In the sepsis group and DEX group,the cecum was ligated and perforated to establish a model.The DEX group was given intraperitoneal injection of 40μg/kg DEX,while the control group and the sepsis group were given the same amount of 0.9% sodium chloride intraperitoneal injection.HE staining was used to directly observe and evaluate the pathological changes of SD rat intestinal mucosa;after the last administration After 24 hours,1.5 ml of blood was collected from the tail vein,and the inflammatory factors interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)pg/ml in serum were determined according to the method in the instructions of the ELISA kit.Western blot was used to detect the expression of Wnt 3a protein,β-catenin(β-catenin),cyclin(cyclin D1),zonula occludens 1(ZO-1)and occludin(Occludin)in intestinal tissue;And the expression results of Wnt 3a protein,β-catenin(β-catenin)cyclin(cyclin D1)were verified by immunohistochemical staining.Results:HE staining observed that the intestinal mucosal damage in the sepsis rats was more serious,while the intestinal mucosal damage in the DEX group was significantly improved.ELISA numerical results showed that the serum levels of interleukin-1β(570.05±83.93),tumor necrosis factor-α(212.34±40.87),and interleukin-6(8.48±0.31)in the sepsis group were significantly higher than those in the control group,while those in the DEX group were significantly higher than those in the control group.The expression levels of these three inflammatory factors were significantly decreased in the sepsis group,and the differences were significant(P <0.05).The gray value analysis of Wb results showed that Wnt 3a(0.296±0.007)and β-catenin(0.259±0.008)in sepsis group and cyclin D1(0.337±0.006)protein expression was significantly higher than the control group,ZO-1(0.259±0.008),Occludin(0.111±0.005)protein expression was significantly lower,the difference was significant(P<0.05),the protein expression levels of Wnt 3a(0.211±0.003),β-catenin(0.322±0.005)and cyclin D1(0.196±0.011)decreased after intraperitoneal injection of DEX,ZO-1(0.58±0.012),Occludin(0.169±0.01))protein expression was increased,and the difference was significant(P<0.05).The results of immunohistochemical staining of Wnt 3a,β-catenin and cyclin D1 were the same as the results of Wb experiment.Conclusion:DEX affects the Wnt/β-catenin signaling pathway and reduces the expression of related inflammatory factors interleukin-1β,tumor necrosis factor-α,and interleukin-6,and increases the expression of tight junction proteins,thereby improving intestinal sepsis and maintaining intestinal mucosal barrier function.