苯烯莫德对炎症性肠病大鼠的疗效及机制研究

Therapeutic efficacy and mechanism of action of benvitimod on the rat colitis model of inflammatory bowel disease

目的 探讨苯烯莫德对炎症性肠病(IBD)大鼠结肠炎的疗效及作用机制.方法 使用葡聚糖硫酸钠(DSS)建立大鼠IBD模型.将SPF级雄性SD大鼠随机分为空白组、IBD模型组、美沙拉嗪治疗组(100 mg/kg·2 d)、苯烯莫德低剂量组(10 mg/kg·2 d)、苯烯莫德高剂量组(20 mg/kg·2 d),每组7只.实验过程中每天记录大鼠的腹泻及血便程度、体质量变化和疾病活动指数(DAI) ,实验结束(第8天)时测量大鼠结肠长度,对结肠组织进行病理评分,检测大鼠白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)含量.结果 与IBD模型组相比较,苯烯莫德高剂量组体质量显著增加(t=8.367,P<0.01)、DAI评分显著降低(t=10.151,P<0.01)、结肠长度显著增加(t=3.160,P=0.008)、结肠组织病理评分显著降低(t=4.323,P=0.001)、血清中IL-6(t=3.321,P=0.02)和TNF-α(t=2.806,P=0.03)含量显著降低;美沙拉嗪组、苯烯莫德低剂量组以及苯烯莫德高剂量组间各项指标差异无统计学意义.实验过程中无大鼠死亡.结论 苯烯莫德能够改善DSS诱导的IBD模型大鼠的症状,疗效与美沙拉嗪相当.

Objective To investigate the therapeutic efficacy and mechanism of action of benvitimod on the rat colitis model of inflammatory bowel disease(IBD).Methods Dextran sulfate sodium(DSS)was used to induce the rat colitis model.A total of 35 rats were randomly divided into five groups(n=7)9 including the control,IBD,mesalazine(100 mg/kg?2 d),benvitimod-low(10 mg/kg?2 d)and benvitimod-high(20 mg/kg?2 d)group.During the experimental period,the score of body weight,bleeding and diarrhea,and disease activity index(DAI)were assessed daily.At the end of the experiment,the length of colon was measured.Colonic tissue was stained with hematoxylin and eosin(HE)fbr histological examination.The enzyme-linked immunosorbent assay(ELISA)was used to determine the concentration of interleukin(IL-6)and tumor necrosis factor(TNF?a)in serum.Results No death was found in each group.At day 8,compared with the IBD group,the benvitimod-high group reversed the lost body weight(t=8.367,P<0.01)and decreased the DAI(t=10.151,P<0.01)and histological scores(t=4.323,P=0.001).The colon in the benvitimod-high group was longer than that in the DSS group(t=3.160,P=0.008).The concentration of IL-6(t=3.321,P=0.02)and TNF-a(t=2.806,P=0.03)in the benvitimod-high group was lower than that in the IBD group.There was no significant difference among the mesalazine,benvitimod-low and benvitimod-high group.Conclusion Benvitimod can ameliorate DSS-Induced colitis in rats and has a similar effect with mesalazine.