葛冰景 曹红燕 戴彦成 阙任烨 傅志泉

〔摘要〕 目的 探討白芍总苷对葡聚糖硫酸钠（dextran sulfate sodium， DSS）诱导的小鼠炎症性肠病（inflammatory bowel disease， IBD）模型的作用及相关机制研究。方法 将50只SPF级C57BL/6小鼠随机分成正常组（N组）、模型组（M组）、柳氮磺吡啶组（L组）、低剂量白芍总苷组（BL组）、高剂量白芍总苷组（BH组），每组10只。M组及治疗组小鼠自由饮用30 g/L DSS，同时予以相应药物灌胃1次;N组自由饮水、进食，连续7 d后处死。期间每天记录小鼠体质量及粪便情况，进行结肠炎疾病活动指数（disease activity index， DAI）评分，利用结肠组织HE染色进行组织病理学评价，利用ELISA法检测血清中IL-8、IL-10、IL-23、IL-36、CCL20、CCR6的表达。结果 与M组比较，用药组DAI评分均显著降低（P<0.05或P<0.01），各用药组之间差异无统计学意义（P>0.05）;与M组比较，用药组均可下调IL-8、IL-23、IL-36、CCL20和CCR6的表达，上调IL-10的表达，并以L组、BH组最为显著（P<0.05或P<0.01）;病理组织学结果显示，L组、BH组结肠组织的炎症反应得到了显著改善。结论 白芍总苷可以有效调节炎症因子表达，减少结肠组织的炎症损伤，并改善小鼠的腹泻及便血症状。

〔关键词〕 白芍总苷;炎症性肠病;葡聚糖硫酸钠;炎症因子;疾病活动指数

〔中图分类号〕R285.5       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2020.08.010

〔Abstract〕 Objective To explore the effect and the underlying mechanism of total glucosides of paeony on inflammatory factors in dextran sulfate sodium （DSS） induced-mice model of inflammatory bowel disease （IBD）. Methods A total of 50 SPF-class C57BL/6 mice were randomly divided into a normal group （N group）， a model group （M group）， a sulfasalazine group （L group）， a low-dose of total glucosides of paeony group （BL group） and high-dose of total glucosides of paeony group （BH group）， with 10 mice in each group. The mice in M group and treatment groups were free to drink 30 g/L DSS， and were given the corresponding medicine by gavage once， while the mice in the N group were free to drink water and eat. All the mice were executed 7 days later. During this period， the status of weight and feces of the mice were recorded， and colitis disease activity index （DAI） score were assessed. In addition， HE staining of colon tissue were performed to evaluate the histopathological injury， and the expression of serum IL-8， IL-10， IL-23， IL-36， CCL20 and CCR6 were determined by using ELISA. Results Compared with the M group， DAI scores of mice in the treatment group were significantly decreased （P<0.05 or P<0.01）， and the differences in each treatment group was not statistically significant （P>0.05）. Compared with the M group， the expression of IL-8， IL-23， IL-36， CCl20， and CCR6 were decreased in the treatment group， while the expression of IL-10 was increased， in which the L group and the BH group were most significant （P<0.05 or P<0.01）. The histopathological results showed that the inflammatory response of colon tissue in the L group and the BH group was significantly improved. Conclusion Total glucosides of paeony could effectively regulate the expression of inflammatory factors， reduce the inflammatory injury of colon tissues， and improve the diarrhea and hematochezia symptoms in mice.

〔Keywords〕 total glucosides of paeony; inflammatory bowel disease; dextran sulfate sodium; inflammatory factor; disease activity index

炎癥性肠病（inflammatory bowel disease， IBD）是一组以腹痛、腹泻、黏液脓血便为主要表现的慢性非特异性肠道炎症性疾病，包括克罗恩病（Crohn's disease， CD）和溃疡性结肠炎（ulcerative colitis， UC）。其病因和发病机制均未明确，目前认为该疾病与遗传、免疫、精神应激等因素相关[1]。由于该病迁延难愈，又易转化为结肠癌，因此被世界卫生组织定义为世界难治病之一，发病率为5/10万～12/10万[2]。我国对此病尚无完整的统计，但就临床所见病例而言并非罕见，且有增多趋势[3]。

根据IBD临床表现的腹泻、腹痛、里急后重、黏液或脓血便等症状，中医学将其归属于“肠癖”“泄泻”“痢疾”“肠风”“脏毒”等范畴[4]，认为其病因与湿热之邪、饮食所伤、情志郁结及禀赋不足等有关，肝郁脾虚为其本，湿热蕴结为其标，并常见本虚标实、寒热错杂之证。……