目的 探討山姜素對葡聚糖硫酸鈉誘導的潰瘍性結(jié)腸炎小鼠的保護作用及其作用機制。方法 C57BL/6小鼠隨機分為對照組、模型組和25、50、100 mg/kg山姜素組。模型組和治療組每天給予3%葡聚糖硫酸鈉溶液，連續(xù)7 d。治療組每日ip生理鹽水0.5 mL+25、50、100 mg/kg山姜素，對照組和模型組每天ip生理鹽水0.5 mL，連續(xù)7 d。觀察小鼠體質(zhì)量變化、結(jié)腸長度、疾病活動指數(shù)（DAI）評分、組織學損傷評分等炎癥反應；透射電鏡觀察腸上皮細胞間連接；免疫組織化學法、Western blotting法檢測腸道緊密連接蛋白claudin-2、occludin、ZO-1、STAT3、pSTAT3、IL-6的表達和STAT3/IL-6信號通路的表達情況。結(jié)果 與模型組比較，山姜素能夠顯著緩解小鼠體質(zhì)量減輕和腸管縮短，降低DAI和組織學評分。山姜素可增強小鼠腸黏膜occludin、ZO-1表達，減弱claudin-2表達，并能夠抑制STAT3/IL-6信號通路。結(jié)論 山姜素能夠上調(diào)葡聚糖硫酸鈉誘導的潰瘍性結(jié)腸炎小鼠結(jié)腸組織occludin、ZO-1的表達，下調(diào)claudin-2的表達，通過調(diào)節(jié)緊密連接蛋白的表達，保護腸上皮細胞屏障的完整性和通透性。通過抑制IL-6/STAT3通路，減輕結(jié)腸炎癥反應。

Objective To study the protective effect of alpinetin on dextran sulfate sodium-induced ulcerative colitis in mice and explain its mechanism. Methods C57BL/6 mice were divided into control group, model group, and apinetin (25, 50, and 100 mg/kg) groups. Mice in model and apinetin groups were given 3% dextran sodium sulfate solution for 7 d. Mice in apinetin groups were ip administered with normal saline 0.5 mL + 25、50、100 mg/kg apinetin, while mice in control and model group were ip administered with normal saline 0.5 mL for 7 d. The body weight, intestinal length, disease activity index (DAI), and histological scores were observed. Epithelial tight junctions were observed by transmission electron microscope. Expression of tight junction claudin-2, occluding, ZO-1, STAT3, pSTAT3, IL-6 in mice and STAT3/IL-6 signaling pathway in the colon were determined by immunohistochemical method and Western blotting method. Results Compared with model group, alpinetin could significantly alleviate body weight loss and intestinal length shortening in mice, reduced DAI and histological scores. In the same time, alpinetin could enhance the expression of occludin and ZO-1 in intestinal mucosa, attenuate claudin-2 expression, and inhibit STAT3/IL-6 signaling pathway. Conclusion Alpinetin can up-regulate the expression of occludin and ZO-1 in the colon tissue of dextran sulfate sodium-induced ulcerative colitis in mice, down regulate the expression of claudin-2, and protect the integrity and permeability of the intestinal epithelial cell barrier by regulating the expression of tight junction. Alpinetin can reduce the colonic inflammatory reaction by inhibiting STAT3/IL-6 signaling pathways.

遼寧省自然科學基金資助項目（20170540529）