替格瑞洛对大鼠溃疡性结肠炎的作用

Effects of ticagrelor on ulcerative colitis in rats

目的建立唑酮诱导的大鼠溃疡性结肠炎(ulcerative colitis,UC)模型,并探究替格瑞洛对该模型的治疗作用及其机制。方法唑酮灌肠建立溃疡性结肠炎大鼠模型。将其随机分为4组,每组7只:正常组,疾病组,柳氮磺胺吡啶组,替格瑞洛组。治疗14 d后处死,ELISA法测定IL-4和IL-10含量;肉眼观察结肠病变,测量结肠湿质量指数,进行结肠病变肉眼大体评分。给药过程中观察大鼠的一般状态,粪便性状和体质量变化。结果疾病组、柳氮磺胺吡啶组大鼠血清IL-10含量较正常组显著降低(45.81±3.25,38.79±4.82 vs 67.01±6.90;均P<0.05),替格瑞洛组血清IL-10含量较疾病组显著升高(54.33±3.41 vs 45.81±3.25;P<0.05)。柳氮磺胺吡啶组大鼠生存时间与正常组、替格瑞洛组存在差异(9.71±1.55 vs 14.00±0.00,14.00±0.00,均P<0.05)。替格瑞洛组、疾病组大鼠的结肠湿质量指数高于正常组(3.86±0.37,5.24±2.13 vs 1.89±0.29,均P<0.05)。结论替格瑞洛短期内虽无法明显缓解临床症状,但可通过免疫调节上调IL-10的含量,有效对抗黏膜损伤,抑制炎症反应,防治并发症,明显改善预后。

Objective To observe therapeutic effects of ticagrelor on oxazolone-induced ulcerative colitis in rats and its mechanisms.Methods Oxazolone was injected through rectum for inducing ulcerative colitis in rats.The rats were randomly assigned to normal group,disease group,sulfasalazine group and ticagrelor group(all n=7).The general status,body weight and fecal character were collected per 3 days.After 21 days’treatment,all the animals were sacrificed and then the amount of IL-4,IL-10 weight of fresh ulcerative tissues were detected,and rectal gross lesions were evaluated.Results Compared with the normal group,disease and sulfasalazine groups showed significant loss of IL-10 in serum(45.81±3.25,38.79±4.82 vs 67.01±6.90;all P<0.05).Serum IL-10 level in the ticagrelor group was significantly different from that in the disease group(54.33±3.41 vs 45.81±3.25;P<0.05).Compared with the normal and ticagrelor groups,there were significant differences in mean survival time in sulfasalazine group(9.71±1.55 vs 14.00±0.00,14.00±0.00,all P<0.05).The index of rectum wet weight in ticagrelor and disease groups were increased compared with the normal group(3.86±0.37,5.24±2.13 vs 1.89±0.29,all P<0.05).Conclusion Through ticagrelor cannot effectively relieve clinical manifestation in short terms,it can modify the immune system through upgrading the level of IL-10,recover the lesions of mucous membrane,control complications and at last improve prognosis.