DPP-4抑制剂治疗小鼠溃疡性结肠炎的疗效

目的 探讨DPP-4抑制剂单独及联合SASP治疗溃疡性结肠炎(UC)小鼠的疗效。方法 30只雄性BALB/c小鼠随机平均分为5组：空白对照组、模型对照组、DPP-4抑制剂治疗组、SASP治疗组、DPP-4抑制剂和SASP联合治疗组(联合治疗组)。除空白对照组外，其他各组均用5%葡聚糖硫酸钠(DSS)诱导小鼠UC模型，空白对照组和模型对照组给予0.5%羧甲基纤维素(CMC)灌胃，DPP-4抑制剂治疗组、SASP治疗组和联合治疗组分别给予西格列汀、SASP、西格列汀和SASP两者联合灌胃治疗，1次/d，连续6d。每天观察小鼠的临床症状，称量小鼠体质量，观察大便形状，检测大便隐血，计算疾病活动指数(DAI)。6d后处死小鼠，分离结肠组织，测量结肠长度，进行病理组织学观察，采用ELISA法检测小鼠血清胰高血糖素样肽-2(GLP-2)水平。结果 与模型对照组相比，DPP-4抑制剂治疗组、SASP治疗组和联合治疗组均明显改善UC小鼠临床症状， DAI评分显著降低(P<0.05)，结肠长度明显增加(P<0.05)，结肠病理损伤明显缓解；DPP-4抑制剂治疗组和联合治疗组血清GLP-2水平显著升高(P<0.01)。与DPP-4抑制剂治疗组比较，联合治疗组小鼠DAI评分显著降低(P<0.05)，结肠长度明显增加(P<0.05)。结论 DPP-4抑制剂对UC小鼠有显著的治疗作用，与SASP联合用药可达到协同的效果。

Therapeutic effect of DPP-4 inhibitor on ulcerative colitis in mice

Objective To explore the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor and DPP-4 inhibitor in combination with sulfasalazine (SASP) on the progression of ulcerative colitis in mice. Methods Thirty male BALB/c mice were randomly divided into five groups: control group, ulcerative colitis group, DPP-4 inhibitor group, SASP group and the combined group. 5% dextran sulfate sodium (DSS) was used to induce the mice models of ulcerative colitis. From the first day of constructing the models, the control group and ulcerative colitis group underwent 0.5% carboxymethylcellulose (CMC) gavage, while DPP-4 inhibitor group, SASP group and the combined group received sitagliptin, SASP, or both respectively. All these treatments were conducted once a day for six days. 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 and serum GLP-2 levels were detected respectively. Results 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); serum GLP-2 levels of the DPP-4 inhibitor group and the combined group were significantly higher (P<0.01). In addition, compared to the DPP-4 inhibitor group, the DAI scores were significantly lower (P<0.01) and the colons were significantly longer (P<0.01). Conclusion DPP-4 inhibitor could effectively treat UC in mice. DPP-4 inhibitor combined with SASP is more effective in treating UC than either agent alone.