低聚原花青素对葡聚糖硫酸钠诱导小鼠溃疡性结肠炎的保护作用

Protective effect of oligomeric proanthocyanidins on dextran sulfate sodium induced ulcerative colitis in mice

目的研究低聚原花青素(oligomeric proanthocyanidins,OPC)对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的溃疡性结肠炎(ulcerative colitis,UC)小鼠的治疗作用,并初步探讨其保护机制。方法选取雄性C57小鼠40只,选取8只为正常对照组。其他32只用2.5%的DSS进行UC造模后,随机分为模型组、美沙拉嗪组(美沙拉嗪500 mg/kg)、低剂量组(OPC500 mg/kg)、高剂量组(OPC1000 mg/kg),每组8只。连续给药7 d后处死小鼠,评估疾病活动指数(DAI),观察结肠病理变化,评估结肠大体形态损伤指数(colon macroscopic damage index,CMDI),计算检测血清IL-10水平,测定髓过氧化物酶(myeloperoxidase,MPO)活性。结果与正常对照组相比,造模后各组小鼠的DAI评分明显升高,结肠黏膜变薄、上皮脱落和炎性细胞浸润,CMDI评分明显升高,结肠长度和血清IL-10水平明显降低,组织MPO活性明显升高,差异有统计学意义(P<0.05);与模型组相比,美沙拉嗪组、低剂量组和高剂量组的DAI评分和CMDI评分显著降低,结肠长度延长,血清IL-10水平明显升高,MPO活性明显降低,差异有统计学意义(P<0.05)。且美沙拉嗪组与高剂量组接近,均优于低剂量组。结论OPC可通过减少氧化应激,抑制炎性反应,降低DSS诱导UC小鼠的DAI,改善小鼠结肠组织病理形态,具有治疗作用。

Objective To investigate the therapeutic effect of oligomeric proanthocyanidins(OPC)against ulcerative colitis(UC)induced by dextran sulfate sodium(DSS)in mice and explore the protective mechanism of OPC.Methods 32 male C57 mice were fed with 2.5%DSS to establish a UC model,which were randomly divided into the model group,treatment control group(mesalazine,500 mg/kg),low dose group(OPC,500 mg/kg)and high dose group(OPC,1000 mg/kg),with 8 mice in each group.At the same time,another 8 male C57 mice were used as the control group and fed with normal water.After 7 days,the mice were sacrificed to evaluate the disease activity index(DAI),observe the pathological changes and evaluate the CMDI,detect the level of serum IL-10 and assay the activity of myeloperoxidase(MPO)in the colon.Results Compared with the normal control group,the DAI score increased significantly,the length of the colon decreased,the colonic mucosa became thinner,the epithelium was exfoliated and inflammatory cells were infiltrated in UC model groups.The level of serum IL-10 decreased significantly,and the activity of MPO improved significantly(P<0.05).Compared with the model control group,the indexes of each group significantly improved(P<0.05),but there was no significant difference between the high dose group and the treatment control group.Conclusions In mice with UC induced by DSS,OPC may help ameliorate DAI and improve the pathological morphology of colon tissue of mice by reducing oxidative stress and inhibiting inflammatory reactions.