目的 探讨低聚葡萄籽原花青素（GSPE）对葡聚糖硫酸钠（DSS）诱导的小鼠溃疡性结肠炎（UC）的影响及作用机制。方法 将SPF级C57小鼠随机分为对照组、模型组、阳性药组（柳氮磺吡啶组）及GSPE低、中、高剂量（125、250、500 mg/kg）组，对照组给予正常饮用水，其他组均自由饮用3% DSS水溶液，连续饮用7 d，诱导小鼠UC模型，每天记录小鼠体质量、便血、便型等症状变化，药物干预治疗7 d后断头取血，收集结肠和脾脏，记录结肠长度、脾脏质量变化情况。HE染色评估小鼠结肠黏膜组织病理变化，ELISA法检测血清和结肠组织中炎症因子白细胞介素-6（IL-6）、IL-1β和肿瘤坏死因子-α（TNF-α）及细胞因子一氧化氮（NO）、丙二醛（MDA）、超氧化物歧化酶（SOD）水平，免疫组化分析结肠组织上皮细胞中血红素加氧酶-1（HO-1）、核转录因子-κB（NF-κB）、转录因子E2相关因子2（Nrf2）及Keap-1蛋白表达水平。结果 与模型组比较，GSPE中、高剂量组小鼠体质量下降相对缓慢，小鼠腹泻、便血症状改善明显；给药后小鼠血清及结肠组织中IL-1β、IL-6、TNF-α、NO、MDA水平较模型组显著降低，SOD水平则显著升高（P<0.01）；病理组织切片分析发现，GSPE高剂量组小鼠结肠黏膜病理损伤显著降低。免疫组化分析结果显示GSPE低、中、高剂量可显著降低NF-κB及Keap-1蛋白表达水平，升高Nrf2、HO-1蛋白表达水平（P<0.01）。结论GSPE能够有效改善DSS诱导的UC症状，通过调节氧化应激相关蛋白Nrf2、HO-1和炎症通路蛋白NF-κB的表达，进而影响氧化应激指标SOD、MDA和炎症因子的变化，降低结肠组织的病理损伤，对UC的治疗与预防具有重要的价值。

Objective To investigate the effect of oligosaccharide grape seed proanthocyanins (GSPE) on dextran sulphate sodium salt (DSS)-induced ulcerative colitis (UC) in mice and its mechanisms. Methods SPF-class C57 mice were randomly divided into normal group, model group, positive group (sulfasalazine group), and GSPE groups (125, 250, 500 mg/kg). The normal group was given pure water, and the other groups were free to drink 3% DSS aqueous solution for 7 d to induce the model of UC in mice. The changes of body weight, hematochezia and stool type were recorded every day. After seven days of treatment, blood, colons and spleens were collected, and the length of the colon and the weight of the spleen were recorded. HE staining was used to evaluate the pathological changes of colonic mucosa in mice. The expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor TNF-α in serum and colon tissues and the levels of NO, MDA, and SOD were detected by ELISA. The changes of HO-1, NF-κB, and Nrf2 in colonic epithelial cells were analyzed by immunohistochemistry. Results Compared with the model group, the body weight of mice in GSPE groups (250, 500 mg/kg) decreased relatively slowly, and the symptoms of diarrhea and hematochezia were improved significantly. The content of IL-1β, IL-6, TNF-α, NO, and MDA in serum and colon tissues was much lower in the administration groups than those in the model group, while the content of SOD was significantly higher (P<0.01). The pathological tissue analysis showed that the pathological damage of colonic mucosa in the high dose group of GSPE was obviously decreased. Immunohistochemical analysis showed that GSPE groups significantly decreased the expression of NF-κB and increased the expression of Nrf2 and HO-1 (P<0.01). Conclusion GSPE could effectively improve the symptoms of UC induced by DSS, and regulate the expression of oxidative stress-related proteins Nrf2, HO-1 and inflammatory pathway protein NF-κB, and then affect the changes of oxidative stress indicators SOD, MDA and inflammatory factors. Therefore, GSPE plays an important role in the treatment and prevention of UC.

国家自然科学基金资助项目（81673693）；武警后勤学院创新团队基金项目（2018）；武警后勤学院博士启动金（WHB201710）