目的 探討低聚葡萄籽原花青素（GSPE）對葡聚糖硫酸鈉（DSS）誘導的小鼠潰瘍性結(jié)腸炎（UC）的影響及作用機制。方法 將SPF級C57小鼠隨機分為對照組、模型組、陽性藥組（柳氮磺吡啶組）及GSPE低、中、高劑量（125、250、500 mg/kg）組，對照組給予正常飲用水，其他組均自由飲用3% DSS水溶液，連續(xù)飲用7 d，誘導小鼠UC模型，每天記錄小鼠體質(zhì)量、便血、便型等癥狀變化，藥物干預治療7 d后斷頭取血，收集結(jié)腸和脾臟，記錄結(jié)腸長度、脾臟質(zhì)量變化情況。HE染色評估小鼠結(jié)腸黏膜組織病理變化，ELISA法檢測血清和結(jié)腸組織中炎癥因子白細胞介素-6（IL-6）、IL-1β和腫瘤壞死因子-α（TNF-α）及細胞因子一氧化氮（NO）、丙二醛（MDA）、超氧化物歧化酶（SOD）水平，免疫組化分析結(jié)腸組織上皮細胞中血紅素加氧酶-1（HO-1）、核轉(zhuǎn)錄因子-κB（NF-κB）、轉(zhuǎn)錄因子E2相關因子2（Nrf2）及Keap-1蛋白表達水平。結(jié)果 與模型組比較，GSPE中、高劑量組小鼠體質(zhì)量下降相對緩慢，小鼠腹瀉、便血癥狀改善明顯；給藥后小鼠血清及結(jié)腸組織中IL-1β、IL-6、TNF-α、NO、MDA水平較模型組顯著降低，SOD水平則顯著升高（P<0.01）；病理組織切片分析發(fā)現(xiàn)，GSPE高劑量組小鼠結(jié)腸黏膜病理損傷顯著降低。免疫組化分析結(jié)果顯示GSPE低、中、高劑量可顯著降低NF-κB及Keap-1蛋白表達水平，升高Nrf2、HO-1蛋白表達水平（P<0.01）。結(jié)論GSPE能夠有效改善DSS誘導的UC癥狀，通過調(diào)節(jié)氧化應激相關蛋白Nrf2、HO-1和炎癥通路蛋白NF-κB的表達，進而影響氧化應激指標SOD、MDA和炎癥因子的變化，降低結(jié)腸組織的病理損傷，對UC的治療與預防具有重要的價值。

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.

國家自然科學基金資助項目（81673693）；武警后勤學院創(chuàng)新團隊基金項目（2018）；武警后勤學院博士啟動金（WHB201710）