阿格列汀治疗三硝基苯磺酸诱导的溃疡性结肠炎小鼠的实验研究

Therapeutic effect of alogliptin on mice with ulcerative colitis induced by trinitrobenzenesulfonic acid

目的观察DPP-4抑制剂Alogliptin对三硝基苯磺酸诱导的溃疡性结肠炎模型小鼠结肠的MPO值,血清IL-8、TNF-α和GLP-2水平的影响,并探讨Alogliptin对炎症性肠病(IBD)的治疗机制。方法雄性BALB/c小鼠48只,分为6组,每组8只,分别为正常对照组、模型组、柳氮磺吡啶治疗组(520 mg/kg),Alogliptin高、中、低剂量组(1、0.3、0.1mg/kg)。模型组采用三硝基苯磺酸(TNBS)对BALB/c小鼠进行灌肠,制作溃疡性结肠炎小鼠模型,经灌胃给予药物治疗后,观察DPP-4酶抑制剂Alogliptin对肠炎小鼠腹泻,组织形态损伤,结肠组织MPO酶活力,血清IL-8、TNF-α和GLP-2含量的影响。结果与模型组相比,Alogliptin高、中剂量组能够改善肠炎小鼠临床症状,减轻结肠黏膜损伤,显著降低TNBS诱导的溃疡性结肠炎小鼠的DAI评分(P<0.01),并且治疗组小鼠结肠组织MPO酶活性、血清IL-8和TNF-α的浓度较模型组显著降低(P<0.05);而Alogliptin治疗组小鼠血清GLP-2的含量较模型组和正常组都有显著升高(P<0.05)。结论 DPP-4酶抑制剂Alogliptin能够有效抑制小鼠肠道炎性细胞的浸润,减轻肠黏膜的病理性损伤,对TNBS诱导的肠炎小鼠具有显著的治疗作用。

Objective To investigate the therapeutic mechanism of dipeptidyl peptidase-4（DPP-4） inhibitor alogliptin on inflammatory bowel disease（IBD） by observing its effects on serum IL-8,TNF-α and GLP-2 levels as well as colonic myeloperoxidase（MPO） activity in mice with ulcerative colitis induced by trinitrobenzenesulfonic acid（TNBS）.Methods Totally 48 male BALB/c mice were equally divided into 6 groups： a normal control group,a model group of IBD,a positive control group with sulfasalazine（520 mg/kg）,and 3 therapeutic groups with high,medium and low alogliptin doses（1,0.3 and 0.1 mg/kg,respectively）.The mice in the model group were treated by rectal instillation with TNBS to establish IBD models and given drugs through intragastric administration to observe the effects of alogliptin on diarrhea,colonic mucosa lesion and colonic MPO activity,as well as serum IL-8,TNF-a and GLP-2 levels in the mice with ulcerative colitis.Results Compared with those of the model group,the clinical symptoms and lesion of colonic mucosa in the therapeutic groups with high and medium alogliptin doses were remarkably improved.In the two groups,the DAI score（P0.01）,colonic MPO activity（P0.05） and serum IL-8 and TNF-α levels（P0.05） decreased significantly.The serum GLP-2 level,however,increased significantly（P0.05） as compared with that of the normal control group or the model group.Conclusion DPP-4 inhibitor alogliptin can effectively inhibit the infiltration of colonic inflammatory cells and alleviate the pathological damage of colonic mucosa,and thus has a significant therapeutic effect on mice with ulcerative colitis induced by TNBS.