目的:炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),与显著的发病率和并发症相关的慢性胃肠道疾病。这项研究调查了二十二碳六烯酸(DHA)在三硝基苯磺酸(TNBS)诱导的结肠炎模型中的治疗潜力,专注于炎症,氧化应激,和肠膜通透性。
方法:Wistar白化病大鼠分为对照组,结肠炎,结肠炎+DHA组(n=8-10/组)。结肠炎和结肠炎+DHA组直肠内接受TNBS,对照组接受生理盐水。通过管饲法施用DHA(600mg/kg/天)或盐水6周。进行结肠组织的宏观和微观评价。参数包括occludin和ZO-1表达式,髓过氧化物酶(MPO)活性,丙二醛(MDA),谷胱甘肽(GSH),总抗氧化剂状态(TAS),总氧化剂状态(TOS),白细胞介素-6(IL-6),在结肠组织中测量肿瘤坏死因子α(TNF-α)水平。
结果:结肠炎诱导导致明显更高的宏观和微观损伤评分,TOS水平升高,减少的occludin和ZO-1强度,粘膜厚度减少,和TAS水平与对照组相比(p<0.001)。DHA给药显著改善了这些参数(p<0.001)。MPO,MDA,TNF-α,和IL-6水平在结肠炎组中升高,但在DHA治疗组中显着降低(MPO的p<0.001,MDA;TNF-α和IL-6的p<0.05)。
结论:DHA通过减少活性氧的产生表现出抗氧化和抗炎作用,增强TAS能力,保持GSH含量,降低促炎细胞因子水平,防止中性粒细胞浸润,减少结肠上皮的脱落,改善腺体结构和粘膜完整性。DHA还上调了对屏障功能至关重要的闭塞蛋白和ZO-1的表达。因此,DHA给药可提供治疗策略或补充以减轻结肠炎诱导的不良反应。
OBJECTIVE: Inflammatory bowel diseases (IBD), including Crohn\'s disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders associated with significant morbidity and complications. This study investigates the therapeutic potential of docosahexaenoic acid (
DHA) in a trinitrobenzene sulfonic acid (TNBS) induced colitis model, focusing on inflammation, oxidative stress, and intestinal membrane permeability.
METHODS: Wistar albino rats were divided into Control, Colitis, and Colitis +
DHA groups (n = 8-10/group). The Colitis and Colitis + DHA groups received TNBS intrarectally, while the Control group received saline.
DHA (600 mg/kg/day) or saline was administered via gavage for six weeks. Macroscopic and microscopic evaluations of colon tissues were conducted. Parameters including occludin and ZO-1 expressions, myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were measured in colon tissues.
RESULTS: Colitis induction led to significantly higher macroscopic and microscopic damage scores, elevated TOS levels, reduced occludin and ZO-1 intensity, decreased mucosal thickness, and TAS levels compared to the Control group (p < 0.001).
DHA administration significantly ameliorated these parameters (p < 0.001). MPO, MDA, TNF-α, and IL-6 levels were elevated in the Colitis group but significantly reduced in the DHA-treated group (p < 0.001 for MPO, MDA; p < 0.05 for TNF-α and IL-6).
CONCLUSIONS: DHA demonstrated antioxidant and anti-inflammatory effects by reducing reactive oxygen species production, enhancing TAS capacity, preserving GSH content, decreasing proinflammatory cytokine levels, preventing neutrophil infiltration, reducing shedding in colon epithelium, and improving gland structure and mucosal membrane integrity.
DHA also upregulated the expressions of occludin and ZO-1, critical for barrier function. Thus, DHA administration may offer a therapeutic strategy or supplement to mitigate colitis-induced adverse effects.