Dietary Red Raspberry Reduces Colorectal Inflammation and Carcinogenic Risk in Mice with Dextran Sulfate Sodium-Induced Colitis.
Dietary Red Raspberry Reduces Colorectal Inflammation and Carcinogenic Risk in Mice with Dextran Sulfate Sodium-Induced Colitis.
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DOI：
10.1093/jn/nxy007
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发表时间：
2018-05-01
期刊：
影响因子：
--
通讯作者：
Zhu MJ
中科院分区：
文献类型：
--
作者：
Bibi S;Du M;Zhu MJ
溃疡性结肠炎会导致复发性肠粘膜损伤和持续性炎症，增加结直肠癌（CRC）发展的可能性。膳食红树莓（RB）是已知具有抗炎活性的植物营养素的丰富来源;然而，RB在慢性结肠炎中对CRC预防的作用尚未研究。本研究检测了膳食RB补充剂对葡聚糖硫酸钠（DSS）诱导的小鼠慢性结肠炎的炎症、上皮修复和致癌信号传导的影响。6周龄雄性C57 BL/6 J小鼠喂食对照或RB（干饲料重量的5%;n = 12/组）饮食10周。从第四周开始，向小鼠施用2个重复周期的1%DSS（7-d DSS治疗加14-d恢复），并每天监测疾病活动指数（DAI）评分。在研究结束时收集结肠组织用于炎症、分化和增殖标记物的组织化学、免疫组织化学和生物化学分析。补充RB可降低DAI评分和组织学损伤（降低38.9%;P ≤ 0.01）、炎症介质表达（降低20-70%;P ≤ 0.01）、CD 4 T细胞浸润（降低50%;P ≤ 0.05）以及α4β7整合素和相关粘附分子（降低33.3%;P ≤ 0.01）。此外，RB补充促进上皮修复，如杯状细胞密度增加、包括Kruppel样因子4（Klf 4）和Hairy和分裂增强子1（Hes 1）在内的转录因子表达增加、终末分化标志物、粘蛋白2（Muc 2）和肠碱性磷酸酶（增加20-200%;P ≤ 0.01）所证明。相反，RB补充降低了增殖细胞核抗原（70%;P ≤ 0.01）、β-连环蛋白和信号转导和转录激活因子3（STAT 3）信号转导（19-33%;P ≤ 0.05）。此外，RB补充增强了p53稳定性（53%）并降低了致癌基因表达（50-60%）。RB补充剂降低了DAI评分和小鼠结肠炎复发期间CRC发展的风险，表明RB是溃疡性结肠炎和相关肠道炎性疾病患者可能的膳食补充剂。
Ulcerative colitis causes recurring intestinal mucosal injury and sustained inflammation, increasing the likelihood of colorectal cancer (CRC) development. Dietary red raspberry (RB) is a rich source of phytonutrients known to have anti-inflammatory activity; however, the role of RB on CRC prevention in chronic colitis has not been examined. This study examined the effects of dietary RB supplementation on inflammation, epithelium repair, and oncogenic signaling in dextran sulfate sodium (DSS)–induced chronic colitis in mice. Six-week-old male C57BL/6J mice were fed a control or RB (5% of dry feed weight;n = 12/group) diet for 10 wk. Starting from the fourth week, mice were administered 2 repeated cycles of 1% DSS (7-d DSS treatment plus 14-d recovery) and were monitored daily for disease activity index (DAI) score. Colonic tissues were collected at the end of the study for histochemical, immunohistochemical, and biochemical analysis of inflammation, differentiation and proliferation markers. RB supplementation reduced the DAI score and histologic damage (by 38.9%;P ≤ 0.01), expression of inflammatory mediators (by 20–70%;P ≤ 0.01), infiltration of CD4 T cells (by 50%;P ≤ 0.05), and α4β7 integrin and related adhesion molecules (by 33.3%;P ≤ 0.01). Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20–200%;P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%;P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19–33%;P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50–60%). RB supplementation reduced DAI score and the risk of CRC development during recurring colitis in mice, suggesting that RB is a possible dietary supplement for patients with ulcerative colitis and related gut inflammatory diseases.
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