摘要
目的:基于肠屏障研究广藿香水提物对溃疡性结肠炎(ulcerative colitis,UC)小鼠改善的作用及机制.方法:将小鼠随机分为空白组、模型组、美沙拉嗪组、广藿香水提物低、高剂量组;自由饮用2.5％葡聚糖硫酸钠(dextran sodium sulfate,DSS)10d诱导小鼠UC模型,造模同时灌胃干预;检测血清白介素6(interleukin-6,IL-6)、白介素1β(IL-1β)和肿瘤坏死因子α(tumor necrosis factor α,TNF-α)水平;苏木素-伊红和高碘酸-席夫染色观察结肠病理变化;免疫组化法检测结肠紧密连接蛋白1(znula ocludens-1,ZO-1)、闭合连接蛋白1(occludin-1)和粘蛋白2(mucin 2,MUC2)蛋白表达;高通量测序技术分析结肠内容物肠道菌群变化.结果:DSS诱导的小鼠经广藿香水提物干预后,血清IL-6、IL-1β和TNF-α水平明显降低(P＜0.05,P＜0.01);结肠炎性浸润、上皮细胞结构破坏和杯状细胞数量减少等病理得到改善;结肠ZO-1、occludin-1和MUC2蛋白表达明显升高(P＜0.05,P≤0.01);肠道菌群α多样性sobs、Shannon和heip指数明显升高(P＜0.05,P＜0.01);肠道菌群β多样性主成分分析、主坐标分析和非度量多维尺度分析趋于健康小鼠;肠道菌群属水平优势物种隆布茨菌属(Romboutsia)、双歧杆菌属(Bifidobacterium)、布劳提菌属(Blautia)和 unclassified_f_Lachnospiraceae 丰度明显纠正(P＜0.05,P＜0.01).结论:广藿香水提物对于DSS诱导的UC小鼠具有明确的改善作用,可能是其通过改善肠屏障而实现.
Abstract
Objective:To explore the ameliorative effects and mechanisms of Pogostemon cablin aqueous extract(PCAE)on mice with ulcerative colitis(UC)based on gut barrier research.Methods:Mice were randomly divided into five groups:Control,model,mesalazine,low-dose of PCAE and high-dose of PCAE groups.A UC model was induced in mice by freely drinking 2.5％dextran sodium sulfate(DSS)for 10 d,with simultaneous oral administration of interventions.The study measured levels of serum interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor α(TNF-α).Pathological alterations in the colon were observed using hematoxylin-eosin and periodic acid-schiff staining.The expression of the colonic tight junction proteins zonula occludens-1(ZO-1),occludin-1,and mucin 2(MUC2)were assessed via immuno-histochemistry.High-throughput sequencing technology was utilized to analyze changes in the gut microbiota of colonic contents.Results:Following intervention with PCAE,DSS-induced mice exhibited a significant reduction in serum levels of IL-6,IL-1β,and TNF-α(P＜0.05,P＜0.01).Pathological improvements in colon inflammation,epithelial cell structural damage,and reduced goblet cell numbers were observed.Additionally,the expression of colonic ZO-1,occludin-1,and MUC2 proteins significantly increased(P＜0.05,P＜0.01).Furthermore,the α-diversity indices of the gut microbiota including sobs,Shannon,and heip exhibited a marked increase(P＜0.05,P＜0.01),while the β-diversity analysis through principal component analysis,principal co-ordinates analysis,and non-metric multidimensional scaling analysis tended towards that of healthy mice.Notably,there was a significant correction in the abundance of dominant species at the genus level,including Romboutsia,Bifidobacterium,Blautia,and unclassified_f_Lachnospiraceae(P≤0.05,P≤0.01).Conclusion:PCAE exhibited a clear ameliorative effect on DSS-induced UC in mice,potentially achieved through the improvement of the gut barrier.
维普
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