Differential effects of EPA and DHA on DSS-induced colitis in mice and possible mechanisms involved
Differential effects of EPA and DHA on DSS-induced colitis in mice and possible mechanisms involved
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EPA 和 DHA 对 DSS 诱导的小鼠结肠炎的不同作用及其可能机制
DOI：
10.1039/d0fo02308f
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发表时间：
2021
期刊：
影响因子：
6.1
通讯作者：
Xiaohong Zhang
中科院分区：
文献类型：
--
作者：
Zhuangwei Zhang;Zhe Xue;Haitao Yang;Feng Zhao;Chundi Liu;Jiahui Chen;Songtao Lu;Zuquan Zou;Yuping Zhou;Xiaohong Zhang
背景n-3多不饱和脂肪酸的抗炎作用已被广泛报道。新的证据表明，n-3多不饱和脂肪酸的主要成分二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)在溃疡性结肠炎(UC)中可能有不同的作用。方法8周龄雄性C57BL/6J小鼠随机分为7组，即对照组、UC模型组、柳氮磺吡啶(SASP)组、低剂量DHA组、高剂量DHA组、低剂量EPA组和高剂量EPA组。DHA、EPA和SASP治疗组分别给予相应的口服治疗9周。第5~9周，对照组给予蒸馏水，其余各组给予蒸馏水加2%葡聚糖硫酸钠(DSS)诱导UC。记录体重减轻、腹泻和大便出血情况，计算疾病活动指数(DAI)。免疫印迹法检测肠上皮细胞紧密连接蛋白Claudin-1、occludin、细胞因子α-β、IL-6、IL-1及炎性细胞标志物MPO、F4/80、MCP-1的表达。同时检测IL-6/STAT3和NLRP3/IL-1β炎症通路的激活情况。结果与DHA相比，EPA明显减轻DSS诱导的结肠炎，表现为DAI评分减少，细胞因子分泌减少，炎细胞浸润明显减少。在机制上，EPA触发了Claudin-1和occludin的显著上调，下调了它们的上游Akt和ERK。EPA还能抑制NLRP3/IL-1β和IL-6/STAT3炎症通路，上调WNT/β-catenin通路。
BackgroundThe anti-inflammatory effect of n-3 PUFAs has been widely documented. Emerging evidence suggests that the main component of n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have differential effects in ulcerative colitis (UC). It was aimed to clarify their differential effects in UC.MethodsEight-week-old male C57BL/6J mice were randomly divided into 7 groups, namely control, UC model, salicylazosulfapyridine (SASP), low-dose DHA, high-dose DHA, low-dose EPA, and high-dose EPA. DHA, EPA and SASP treatment groups were orally treated accordingly for 9 weeks. During the 5th to 9th week the control group was given distilled water, while other groups were given distilled water with 2% dextran sodium sulfate (DSS) to induce UC. Body weight loss, diarrhea, and stool bleeding were recorded to calculate the disease activity index (DAI). The level of tight junction proteins Claudin-1 and Occludin, and cytokines including TNF-α, IL-6, and IL-1β as well as inflammatory cell markers such as MPO, F4/80, and MCP-1 in the intestinal epithelium were measured using western blotting. Activation of IL-6/STAT3 and NLRP3/IL-1β inflammatory pathways was also assessed. Levels of proliferation-related proteins of the Wnt/β-catenin pathway with c-myc, Cyclin-D1, and PCNA were detected.ResultsEPA, superior to DHA, significantly attenuated DSS-induced colitis evidenced by reduced DAI scores, cytokine production and inflammatory cell infiltration. Mechanically, EPA triggered a marked up-regulation of Claudin-1 and Occludin with down-regulation of their up-stream Akt and ERK. EPA also inhibited NLRP3/IL-1β and IL-6/STAT3 inflammatory pathways and up-regulated the Wnt/β-catenin pathway.ConclusionsEPA is more suitable to be used for the treatment of UC than DHA.