Effects Of Dexmedetomidine On Intestinal Mucosa In Septic Rats Mediated By Wnt/β-catenin Pathway

Objective:To investigate the effects of dexmedetomidine(DEX)on intestinal mucosa of sepsis rats and its mechanism.Methods:Forty rats were randomly divided into sepsis group and DEX group,with 20 rats in each group.Septic models in the sepsis group and the DEX group were induced with cecal ligation and puncture(CLP).Another 20 rats were selected as the control group,which only underwent laparotomy without cecal ligation and puncture.The DEX group was given intraperitoneal injection of 40ug/kg DEX immediately after CLP model was established.Sepsis group and control group were intraperitoneal injection of 0.9% Na Cl with equal volume.Ileum injury was assessed pathologically in all three groups.Plasma levels of procalcitonin(PCT)and C-reactive protein(CRP)were detected by ELISA,and the expression levels of Wnt1,β-catenin,intestinal apoptosis-related proteins Bax,Bcl-2and Caspase-3 were analyzed by Western-blot(WB)and immunohistochemistry.Results:Pathological microscopic results showed that the intestinal mucosa was significantly damaged in sepsis group and slightly damaged in DEX group.The Chui’s scores of intestinal mucosa in control group,sepsis group and DEX group were(0.44±0.25),(4.54±1.34)and(0.44±0.25).The difference between sepsis group and control group and DEX group was statistically significant(P < 0.05).The results of ELISA showed that the PCT levels of the three groups were(261.16±15.23),(1131.41±100.75)and(825.57±89.13)pg/ml;the CRP levels were(119.39±14.43),(842.76±101.27),(334.10±50.87)ng/ml.The inflammatory indexes of sepsis group were significantly higher than those of the control group,and the DEX group treated with DEX was significantly lower than that of sepsis group(P < 0.05).Western blot showed that the anti apoptotic Bcl-2 protein of the three groups were(0.524±0.009),(0.157±0.005)and(0.305±0.003);the expressions of pro apoptotic Bax protein were(0.082±0.008),(0.308±0.009)and(0.218±0.01);the expressions of pro apoptotic Caspase-3 protein were(0.115±0.009),(0.498±0.009)and(0.325±0.015);the expressions of Wnt1 were(0.132±0.011),(0.496±0.023)and(0.261±0.006);the expressions of β-catenin were(0.103±0.003),(0.601±0.02)and(0.464±0.011).Compared with the control group and the DEX group,the above indexes in sepsis group had statistically significant differences(all P < 0.05).Conclusion:DEX has a protective effect on ileum injury in septic rats,which may normalize the apoptosis-related protein Bcl-2/Bax ratio by regulating the Wnt/β-catenin signaling pathway,thus reducing the oxidative stress,inflammatory response and apoptosis of intestinal epithelium during sepsis.