ABSTRACT
Objective To investigate the mechanism of Gentianopsis paludosa xanthone(GPX)combined with probiotics in the intervention of colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors.Methods Ninety rats were divided into the normal group,the model group[drinking sodium dextran sulfate(DSS)for 3 days]and the intervention group by random number table method.The model group was subdivided into the inflammatory stage group,the pre-inflammatory cancer group(DMH injection for 4 weeks),the intermediate inflammatory cancer group(DMH injection for 13 weeks)and the advanced inflammatory cancer group(DMH injection for 21 weeks).The administration group was subdivided into the groups(after the first day of drinking DSS,drugs for each group were given by gavage once a day for 8 weeks)on the basis of the advanced inflammatory cancer group,including the GPX group(GPX 69.3 mg/kg),the probiotic group,the combined group(GPX+probiotics 400 mg/kg)and the thalidomide group(thalidomide 13.5 mg/kg).The disease activity index(DAI),colon length and wet mass index were compared between all groups.Characteristics of colon tumors were observed,and pathological changes of colon were observed by HE staining.The expression levels of transforming growth factor(TGF)-β1,Smad4,Smad7,interleukin(IL)-6 and tumor necrosis factor(TNF)-α were detected by Western blot assay and enzyme-linked immunosorbent assay,respectively.Results Compared with the advanced inflammatory cancer group,the administration groups showed an increase in colon length,the expression levels of TGF-β1 and Smad4 protein,a decrease in colon wall thickness,wet mass index,maximum tumor diameter,the levels of Smad7,IL-6,TNF-α,and DAI score decreased in the GPX group and the combined group(P＜0.05).The structure and morphology of intestinal mucosa were improved in the GPX group,the probiotic group and the combination group,and the structure of colonic crypt and goblet cell number were increased.Compared with the probiotic group and the GPX group,the colon wall thickness,colon wet mass index and tumor number were decreased,the protein expression levels of TGF-β1 and Smad4 were increased,and levels of IL-6 and TNF-α were decreased in the combination group(P＜0.05).Conclusion GPX combined with probiotics could inhibit the transformation of colon inflammation-tumor,and the mechanism may be related to the regulation of TGF-β1/Smads pathway and the inhibition of pro-inflammatory factors of IL-6 and TNF-α.