Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages
Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages
复制标题
青蒿素类似物 SM934 通过抑制中性粒细胞和巨噬细胞改善 DSS 诱导的小鼠溃疡性结肠炎
DOI：
10.1038/aps.2017.185
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发表时间：
2018-10-01
影响因子：
8.2
通讯作者：
Zuo, Jian-ping
中科院分区：
文献类型：
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作者：
Yan, Yu-xi;Shao, Mei-juan;Zuo, Jian-ping
溃疡性结肠炎(UC)是一种慢性、非特异性炎症性肠病(IBD)，其特征是复杂的、反复发作的胃肠道炎症。SM934是一种具有抗炎和免疫调节作用的水溶性青蒿素类似物。在本研究中，我们观察了SM934对活体和体外UC的影响。用5%葡聚糖硫酸钠(DSS)灌胃建立小鼠结肠炎模型。给小鼠灌胃SM934(3，10 mg/(kg·d)，ig)，连续10天。处死小鼠后，收集结肠、脾和肠系膜淋巴结(MLN)进行分析。我们发现，SM934给药恢复了DSS诱导的体重减轻、结肠缩短、损伤和炎症评分。此外，SM934还能显著降低结肠组织的疾病活动指数(DAI)、组织病理学评分和髓过氧化物酶(MPO)活性。此外，SM934剂量依赖地降低DSS诱导的促炎细胞因子(IL-1β、IL-6和肿瘤坏死因子-α)的基因和蛋白水平以及结肠组织中巨噬细胞和中性粒细胞的百分比。体外检测SM934对内毒素刺激的RAW 264.7细胞和THP-1来源的巨噬细胞的影响。SM934(0.8、8、80μ摩尔/L)通过抑制NF-κB信号的激活，剂量依赖性地减少脂多糖刺激的RAW264.7细胞和THP-1来源的巨噬细胞中促炎介质的产生。结果表明，SM934对DSS诱导的结肠炎的保护作用可能与其抑制中性粒细胞和巨噬细胞以及抑制NF-κB信号通路有关，提示SM934可能是一种治疗溃疡性结肠炎的有效药物。
Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease (IBD) characterized by complicated and relapsing inflammation in the gastrointestinal tract. SM934 is a water-soluble artemisinin analogue that shows anti-inflammatory and immuno-regulatory effects. In this study, we investigated the effects of SM934 on UC bothin vivoandin vitro. A mouse model of colitis was established in mice by oral administration of 5% dextran sulfate sodium (DSS). SM934 (3, 10 mg/kg per day, ig) was administered to the mice for 10 days. After the mice were sacrificed, colons, spleens and mesenteric lymph nodes (MLNs) were collected for analyses. We showed that SM934 administration restored DSS-induced body weight loss, colon shortening, injury and inflammation scores. Furthermore, SM934 administration significantly decreased the disease activity index (DAI), histopathological scores, and myeloperoxidase (MPO) activities in colonic tissues. Moreover, SM934 administration dose-dependently decreased the mRNA and protein levels of DSS-induced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the percentage of macrophages and neutrophils in colon tissues. The effects of SM934 on LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages were examined in vitro. Treatment with SM934 (0.8, 8, 80 μmol/L) dose-dependently decreased the production of pro-inflammatory mediators in LPS-stimulated RAW264.7 cells and THP-1-derived macrophages via inhibiting activation of the NF-κB signaling. Our results reveal the protective effects of SM934 on DSS-induced colitis can be attributed to its suppressing effects on neutrophils and macrophages and its inhibitory role in the NF-κB signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.