Therapeutic Effect Of DPP-4Inhibitor On Ulcerative Colitis In Mice

Objective1. To explore the effect of DPP-4inhibitor on ulcerative colitis in mice.2. To explore whether there is synergistic effect when DPP-4inhibitor is combined with SASP against ulcerative colitis in mice.3. To explore the mechanisms underlying therapeutic effects of DPP-4inhibitor against ulcerative colitis in mice through detection of serum levels of TNF-α,IL-10and GLP-2using the method of ELISA.MethodsThirty male BALB/c mice were randomly divided into five groups:control group, ulcerative colitis group, DPP-4inhibitor group, SASP group and the combined group.5%dextran sulfate sodium was used to induce the mice models of ulcerative colitis. From the first day of constructing the models, control group and ulcerative colitis group underwent0.5%carboxymethylcellulose gavage, while DPP-4inhibitor group, SASP group and the combined group received sitagliptin, SASA, or both respectively. All these treatments were conducted once a day for six days. Clinical symptoms of all mice were recorded. Body weight, characteristics of stool, and the presence of blood in the stools were measured every day to assess the disease activity index (DAI) scores. Six days later, all mice were sacrificed. The colon length, colon pathological changes, the myeloperoxidase (MPO) activity of colon, and the serum levels of TNF-a,IL-10and GLP-2were detected respectively.ResultsCompared to the control group, there are weight lower, diarrhea, bloody stools, less moving, listlessness, hair scattered and other clinical symptoms on mice in the ulcerative colitis group, and the colon pathological lesion was more serious, the DAI scores were significantly higher (P<0.01), the colons were significantly shorter (P<0.01), the MPO activity of colon and serum TNF-α,IL-10,GLP-2levels were significantly higher (P<0.01). Compared to the ulcerative colitis group, the clinical symptoms and the colon pathological lesion in all three treatment groups were significantly attenuated, the DAI scores were significantly lower (P<0.05), the colons were significantly longer (P<0.05), the MPO activity of colon and serum TNF-α levels were significantly lower (P<0.01); serum GLP-2levels of DPP-4inhibitor group and the combined group were significantly higher (P<0.01); serum IL-10levels of SASP group and the combined group were significantly higher (P<0.01). Compared to DPP-4inhibitor group, the DAI scores of the combined group were significantly lower (P<0.05), the colons were significantly longer (P<0.05), the MPO activity of colon was significantly lower(P<0.05), serum TNF-α levels were significantly lower (P<0.01), and serum IL-10levels were significantly higher (P<0.01). Compared to SASP group, the MPO activity of colon and serum TNF-α levels of the combined group were significantly lower(P<0.05), serum GLP-2levels were significantly higher (P<0.01). There is no significant change (P>0.05) of the DAI scores, the colon length and the MPO activity of colon between DPP-4inhibitor group and SASP group. But the serum TNF-α levels were significantly lower (P<0.05), serum IL-10levels were significantly higher (P<0.01),and serum GLP-2levels were significantly lower (P<0.01) in SASP group compared to DPP-4inhibitor group.ConclusionsDPP-4inhibitor can effectively treat ulcerative colitis in mice. DPP-4inhibitor has a synergistic effect with SASP possibly by up-regulating serum level of GLP-2and exerting an anti-inflammatory effect independent of IL-10.