背景:溃疡性结肠炎(UC)是一种慢性非特异性炎症性肠病,到目前为止,UC的治疗剂仍不能发挥满意的作用。因此,本研究旨在探讨乳香酸包覆锌纳米颗粒(BAs-ZnNPs)对葡聚糖硫酸钠(DSS)诱导的大鼠UC的改善作用。
方法:大鼠分为5组,BAs-ZnNPs,DSS,DSS+BA,和DSS+BAs-ZnNPs。比色法测定碱性磷酸酶(ALP)活性,而IgM的浓度,IgG,TNF-α,IL-1β,用ELISA法测定IL-8。通过RT-qPCR评估NF-κB和COX-2基因的基因表达水平,而PI3K和STAT-3的蛋白表达水平通过蛋白质印迹法进行。最后,对不同组大鼠的结肠组织进行组织病理学检查。
结果:在TEM图像中描绘的直径为50至100nm的尺寸范围内的BAs-ZnNP的球状结构,而它们的形成通过UV-可见光谱法证实,在266nm处具有最大吸光度的尖峰。我们的结果表明,BAs-ZnNPs在结肠炎实验模型中发挥抗炎作用,如ALP的改善所示,在组织学和生物化学上证明,IgM,IgG,以及NF-κB和COX-2的基因表达水平。此外,这种有益作用与TNF-α表达的降低有关,IL-1β,IL-8,PI3K,和STAT-3。因此,这种作用改善了与结肠炎症相关的改变的免疫反应。
结论:BAs-ZnNPs可以作为治疗候选药物来减轻UC。潜在的潜在机制包括抑制ALP,IgM,IgG,IL-1β,和IL-8水平通过调节NF-κB和COX-2基因表达以及STAT-3和PI3K蛋白表达在UC大鼠模型中。
BACKGROUND: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, and until now therapeutic agents for UC still cannot exert satisfied effects. Therefore, this study aimed to investigate the ameliorative effect of boswellic acid coated zinc nanoparticles (BAs-ZnNPs) on dextran sodium sulphate (DSS) induced-UC in rats.
METHODS: Rats were divided into five groups; control, BAs-ZnNPs, DSS, DSS+BAs, and DSS + BAs-ZnNPs. The activity of alkaline phosphatase (ALP) was determined colorimetrically, while the concentration of IgM, IgG, TNF-α, IL-1β, and IL-8 were measured by ELISA. Levels of gene expression of NF-κB and COX-2 genes were evaluated by RT-qPCR, while the expression of protein levels of PI3K and STAT-3 were done by western blotting. Finally, histopathological examination of colon tissues of different groups of rats was done.
RESULTS: The depicted ball-like structure of the BAs-ZnNPs in the TEM images ranging in size from 50 to 100 nm in diameter while their formation was confirmed by UV-visible spectroscopy with a sharp peak of maximum absorbance at 266 nm. Our results revealed that BAs-ZnNPs exerted an anti-inflammatory effect in the experimental model of colitis, demonstrated histologically and biochemically as shown by the improvement of ALP, IgM, IgG, and the gene expression levels of NF-κB and COX-2. Also, this beneficial effect was associated with the reduction in the expression of TNF-α, IL-1β, IL-8, PI3K, and STAT-3. Thus, this effect improves the altered immune response associated with the colonic inflammation.
CONCLUSIONS: BAs-ZnNPs can be proposed as a therapeutic candidate to attenuate UC. The potential underlying mechanism includes suppression of ALP, IgM, IgG, IL-1β, and IL-8 levels via regulation of NF-κB and COX-2 gene expression and STAT-3 and PI3K protein expression in a UC rat model.