Abstract：
Our previous research indicated that Sodium houttuyfonate (SH) can effectively ameliorate dextran sulfate sodium (DSS)-induced colitis exacerbated by Candida albicans. However, the underlying protective mechanism of SH remains unclear. Therefore, in this study, a mice colitis model was infected with C. albicans, and the total colonic miRNAs were assessed. Furthermore, the differentially expressed miRNAs were enriched, clustered, and analyzed. Moreover, based on the dual luciferase analysis of NFKBIZ modulation by miR-32-5p, the in vitro and in vivo therapeutic effects of SH on inflammatory response, fungal burden, oxidative stress, and apoptosis were assessed at transcriptional and translational levels in the presence of agonist and antagonist. A total of 1157 miRNAs were identified, 84 of which were differentially expressed. Furthermore, qRT-PCR validated that SH treatment improved 17 differentially expressed miRNAs with > fourfold upregulation or > sixfold downregulation. Similar to most differentially altered miRNA, C. albicans significantly increased Dectin-1, NF-κB, TNF-α, IL-1β, IL-17A, and decreased miR-32-5p which negatively targeted NFKBIZ. In addition, SH treatment reduced inflammatory response and fungal burden in a colitis model with C. albicans infection. Further analyses indicated that in C. albicans infected Caco2 cells, SH inhibited fungal growth, oxidative stress, and apoptosis by increasing Dectin-1, NF-κB, NFKBIZ, TNF-α, IL-1β, IL-17A, and decreasing miR-32-5p. Therefore, SH can ameliorate the severity of colitis aggravated by C. albicans via the Dectin-1/NF-κB/miR-32-5p/NFKBIZ axis.
摘要：
我们先前的研究表明鱼腥草素钠（SH）可以有效改善葡聚糖硫酸钠（DSS）诱导的白色念珠菌加重的结肠炎。然而,SH的潜在保护机制尚不清楚。因此,在这项研究中，小鼠结肠炎模型感染白色念珠菌，和总的结肠miRNAs进行评估。此外，差异表达的miRNA被富集，集群，并分析。此外，基于miR-32-5p对NFKBIZ调节的双荧光素酶分析，SH对炎症反应的体外和体内治疗作用，真菌负荷，氧化应激，在激动剂和拮抗剂的存在下，在转录和翻译水平上评估细胞凋亡。总共鉴定出1157个miRNAs,其中84个差异表达。此外，qRT-PCR验证了SH处理改善了17种差异表达的miRNA,其中>4倍上调或>6倍下调。与大多数差异改变的miRNA相似，白色念珠菌显著增加Dectin-1、NF-κB、TNF-α,IL-1β,IL-17A,和减少miR-32-5p，其负向靶向NFKBIZ。此外,SH治疗减少了白色念珠菌感染的结肠炎模型中的炎症反应和真菌负担。进一步的分析表明，在白色念珠菌感染的Caco2细胞，SH抑制真菌生长，氧化应激，通过增加Dectin-1，NF-κB，NFKBIZ,TNF-α,IL-1β,IL-17A,并降低miR-32-5p。因此,SH可以通过Dectin-1/NF-κB/miR-32-5p/NFKBIZ轴改善白色念珠菌加重的结肠炎的严重程度。
