Abstract：
As a dietary supplement, hyaluronic acid (HA) has exhibited appreciable immunomodulatory activity and an ameliorative effect on rodent colitis. However, its high viscosity is not only refractory to absorb through the gut, but also causes flatulence. In contrast to HA, hyaluronic acid oligosaccharides (o-HAs) can overcome the above-mentioned constraints, but their treatment effect still remains ill-defined contemporarily. Herein, the current study intends to compare the modulatory effects of HA and o-HA on colitis and assess the underlying molecular mechanism. We first showed that o-HA had a better preventive effect than HA in alleviating colitis symptoms, as evidenced by lower body weight loss, lower disease activity index scores, a lower inflammatory response (TNF-α, IL-6, IL-1β, p-NF-κB), and more intact colon epithelial integrity in vivo. The best efficiency was observed in the o-HA treated group with a dosage of 30 mg kg-1. In an in vitro barrier function assay, o-HA exerted a better protective effect on the transepithelial electrical resistance (TEER), FITC permeability, and wound healing and modulated the expression of tight junction (TJ) proteins (ZO-1, occludin) in lipopolysaccharide (LPS)-stimulated Caco-2 cells. In summary, both HA and o-HA showed the potential to reduce inflammation and ameliorate intestinal damage in DSS-induced colitis and LPS-induced inflammation, but o-HA had improved outcomes. The results also provided a glimpse of the latent mechanism by which HA and o-HA enhanced intestinal barrier function via MLCK/p-MLC signaling pathway suppression.
摘要：
作为膳食补充剂，透明质酸（HA）对啮齿动物结肠炎具有明显的免疫调节活性和改善作用。然而,它的高粘度不仅难以通过肠道吸收，但也会导致肠胃胀气。与HA相比，透明质酸寡糖(o-HAs)可以克服上述限制，但是他们的治疗效果仍然不明确。在这里，本研究旨在比较HA和o-HA对结肠炎的调节作用,并评估其潜在的分子机制.我们首先发现o-HA在缓解结肠炎症状方面比HA具有更好的预防作用，下体体重减轻证明了这一点，较低的疾病活动指数得分，较低的炎症反应（TNF-α，IL-6，IL-1β，p-NF-κB），体内更完整的结肠上皮完整性。在剂量为30mgkg-1的o-HA治疗组中观察到最好的效率。在体外屏障功能测定中，o-HA对跨上皮电阻(TEER)有较好的保护作用,FITC渗透率,和伤口愈合，并调节了脂多糖（LPS）刺激的Caco-2细胞中紧密连接（TJ）蛋白（ZO-1，occludin）的表达。总之,HA和o-HA在DSS诱导的结肠炎和LPS诱导的炎症中显示出减少炎症和改善肠道损伤的潜力，但o-HA的结局有所改善.结果还提供了对HA和o-HA通过MLCK/p-MLC信号传导途径抑制增强肠屏障功能的潜在机制的一瞥。
