Abstract：
Ulcerative colitis (UC) is a prominent category of disease that is associated with bowel inflammation, it can occur at any period of life and is prevalently rising on a global scale. Dextran sulfate sodium (DSS) has been extensively used to develop colitis due to its ability to mimic human UC, providing consistent and reproducible inflammation, ulceration, and disruption of the epithelial barrier in the colon. Chronic inflammation in the gut can lead to alterations in the gut-liver axis, potentially impacting liver function over time, while direct evidence linking diversion colitis to liver damage is limited. Thus, the present study aims to assess the gut and liver damage against DSS and the possible molecular mechanisms. Forty-seven animals were randomly assigned to six groups. Ulcerative colitis was induced using 2.5% w/v DSS in three alternate cycles, each lasting 7 days, with 1-week remission periods in between. SOV (5 and 10 mg/kg, orally) and the standard drug 5-aminosalicylic acid (100 mg/kg, orally) were administered from the start of the 2nd DSS cycle until the end of the experiment. Biochemical parameters, ELISA, histopathological, and immunohistochemical analyses have been conducted to assess damage in the colon and liver. SOV significantly reduced colitis severity by lowering the DAI score, oxidative stress markers (LPS, IL-1β, MPO, nitrite), and restoring liver biomarkers (SGPT, SGOT). Histopathological findings supported these protective benefits in the liver and gut. Moreover, immunohistochemical analysis showed SOV enhanced the expression of the cytoprotective mediator Nrf2/Keap-1 and reduced the expression of inflammatory mediators NF-κB and IL-6. Present findings concluded that SOV demonstrated a dose-dependent effect against UC through anti-inflammatory and antioxidant pathways, with the highest dose of SOV 10 mg/kg having more significant (p < 0.001) results than the low dose of 5 mg/kg.
摘要：
溃疡性结肠炎（UC）是一种与肠道炎症相关的突出疾病，它可以发生在生命的任何时期，并且在全球范围内普遍上升。葡聚糖硫酸钠（DSS）由于其模仿人类UC的能力而被广泛用于发展结肠炎，提供一致和可重复的炎症，溃疡,以及结肠上皮屏障的破坏.肠道慢性炎症可导致肠-肝轴的改变，随着时间的推移可能会影响肝功能，而将转移性结肠炎与肝损害联系起来的直接证据是有限的。因此，本研究旨在评估针对DSS的肠道和肝脏损害以及可能的分子机制。将47只动物随机分配到6组。在三个交替周期中使用2.5％w/vDSS诱导溃疡性结肠炎，每次持续7天，在1周的缓解期之间。SOV（5和10mg/kg，口服）和标准药物5-氨基水杨酸（100mg/kg，口服）从第二个DSS周期开始直到实验结束。生化参数,ELISA,组织病理学,和免疫组织化学分析已进行，以评估结肠和肝脏的损伤。SOV通过降低DAI评分显着降低结肠炎的严重程度，氧化应激标志物(LPS，IL-1β,MPO,亚硝酸盐),和恢复肝脏生物标志物(SGPT，SGOT）。组织病理学发现支持肝脏和肠道中的这些保护性益处。此外，免疫组织化学分析显示SOV增强了细胞保护介质Nrf2/Keap-1的表达，并降低了炎症介质NF-κB和IL-6的表达。目前的研究结果得出结论，SOV通过抗炎和抗氧化途径对UC表现出剂量依赖性作用，最高剂量的SOV10mg/kg比低剂量5mg/kg具有更显著的结果(p<0.001)。
