Effect and mechanism of gliclazide on intestinal mucosal barrier function in rats with ulcerative colitis
Objective To investigate the effect of gliclazide(GLZ)on intestinal mucosal barrier function in rats with ulcerative colitis(UC)by regulating advanced glycation end-products(AGEs)and their receptor for advanced glyca-tion end-products(RAGE).Methods The UC rat model was established by using trinitrobenzene sulfonic acid and alco-hol enema.They were randomly divided into the blank group,UC group,GLZ group(10 mg/kg GLZ),GLZ + empty vec-tor group(10 mg/kg GLZ + 0.15 μL lentiviral empty vector),and GLZ + RAGE overexpression group(10 mg/kg GLZ+ 0.15 μL RAGE overexpression lentiviral vector).After the intervention,the general conditions of the rats in each group were observed,the body weight was measured,and disease activity index(DAI)score was performed.Blood samples were collected and the levels of diamine oxidase(DAO)and D-lactic acid(D-LA)in serum were detected.Colon tissue was se-lected and the pathological damage score was performed.Myeloperoxidase(MPO)activity,and the protein expression lev-els of AGE,RAGE,phosphorylated nuclear transcription factor p65(p-NF-κB p65)and NF-κB p65 were determined.Results Compared with the blank group,the DAI and colon histopathological scores increased,the levels of DAO and D-LA in serum increased,MPO activity,and the expression levels of RAGE,AGE,and p-NF-κB p65/NF-κB p65 increased in the UC group.Compared with the UC group,the DAI and pathological scores,the levels of DAO and D-LA in serum,MPO activity,the expression levels of RAGE,AGE,and p-NF-κB p65/NF-κB p65 decreased in the GLZ group and the GLZ+empty vector group.Compared with the GLZ+empty vector group,the DAI and pathological scores,the level of DAO and D-LA in serum,MPO activity,the expression levels of RAGE,AGE,and p-NF-κB p65/NF-κB p65 increased in the GLZ+RAGE overexpression group.The differences between the above observation groups were statistically significant(all P<0.05).Conclusion GLZ can improve the symptoms of pathological injury in UC rats and protect the intestinal muco-sal barrier function,which may be related to the inhibition of AGE/RAGE signaling pathway.
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