The Effects And Mechanisms Of Total Glucosides Of Paeony To Mouse Ulcerative Colitis

Objiective：To study the effects of total glucosides of paeony（TGP） onNF-κB p65、TNF-、occludin、MFG-E8in the intestinal mucosa of the acutestage ulcerative colitis mice which induced by Dextran Sulfate Sodium (DSS)and evaluate the effectiveness of TGP in ulcerative colitis (UC) therapy.Methods： Fifty-four mice were equally, randomly divided into6groups(n=9), normal control group, model control group,salazosulfapyridine(SASP) group(300mg·kg-1·d-1), low-dose TGPgroup(60mg·kg-1·d-1), medium-dose TGP group(120mg·kg-1·d-1) andhigh-dose TGP group(240mg·kg-1·d-1). The normal control group was givendistilled water, while other groups were only given5%DSS solution(weight/volume) for7days to induce the acute ulcerative colitis. After that,the normal control group and model control group were perfused a stomacheach with0.5ml of distilled water for7days, while other groups wereperfused a stomach with the same dose of the drug solution to treat for7days.Then, we graded each group by disease activity index(DAI), histologicalindex(HI) and measured the level of Nuclear factor-kappaB p65（NF-κBp65）,tumor necrosis factor-（TNF-）,occludin, Milk fat globule-epidermalgrowth factor8（MFG-E8）by immunohistochemistry.Results:1From the DAI score in the first day treatment, compared each group ofmodel control group, SASP group，low-dose TGP,medium-dose TGP group,high-dose TGP group had no statistical significance (p>0.05). 2After7days treatment，compared with the model control group,theDAI score and HI score were significantly decreased in SASP group，medium-dose TGP group, high-dose TGP group (p<0.05),but was similar tothat in the low-dose TGP(p>0.05). These scores of high-dose TGP group werelower than SASP group, medium-dose TGP group(p<0.05),while SASP groupand medium-dose TGP group had no statistical significance (p>0.05).3Compared with the model control group, the expressions of NF-κBp65, TNF-, occludin, MFG-E8of intestinal mucosa had statisticalsignificance in normal control group, SASP group，medium-dose TGP group,high-dose TGP group (p<0.05),but was similar to that in the low-doseTGP(p>0.05). Compared with SASP group, medium-dose TGP group andhigh-dose TGP group, the expressions of them had statistical significance(p<0.05). Compared SASP group and medium-dose TGP group, the resultshad no statistical significance (p>0.05), and the same to the normal controlgroup and high-dose TGP group (p>0.05).4Pearson correlation analysis revealed that average grayscale value ofMFG-E8highly and negatively correlated with average grayscale value ofNF-κB p65（r=-0.944,p<0.01）.Conclusion： TGP has certain therapeutic effects on experimentalulcerative colitis and is related to the TGP dosage, the high-dose TGP is thebest,and the low-dose TGP is the worst.The effect of medium-dose TGP andSASP is similar.It may be achieved by its inhibitory effect on the expressionsof NF-κB p65and TNF-, which is beneficial to restore intestinal mucosabarrier structure by up-degrading the expressions of occludin and MFG-E8.