白藜芦醇通过增强自噬缓解葡聚糖硫酸钠诱导的结肠炎小鼠肠黏膜屏障功能障碍。

BACKGROUND: Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis (UC). Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice. Resveratrol exerts anti-inflammatory functions by regulating autophagy. AIM: To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis mice. METHODS: Male C57BL/6 mice were divided into four groups: negative control group, DSS model group, DSS + resveratrol group, and DSS + 5-aminosalicylic acid group. The severity of colitis was assessed by the disease activity index, serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay. Colon tissues were stained with haematoxylin and eosin, and mucosal damage was evaluated by mean histological score. The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis. In addition, the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot, and morphology of autophagy was observed by transmission electron microscopy. RESULTS: The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42, 3.81, and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α, interleukin-6 and interleukin-1β, respectively, in DSS-induced colitis mice compared with DSS group ( < 0.05). The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased, and were increased in resveratrol-treated colitis group. Resveratrol also increased the levels of LC3B (by 1.39-fold compared with DSS group) and Beclin-1 (by 1.49-fold compared with DSS group) ( < 0.05), as well as the number of autophagosomes, which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy. CONCLUSION: Resveratrol treatment decreased the expression of inflammatory factors, increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction; this effect may be achieved by enhancing autophagy in intestinal epithelial cells.

背景：肠黏膜屏障功能障碍在溃疡性结肠炎（UC）发病机制中起重要作用。最近的研究表明，自噬受损与结肠炎小鼠黏膜中的肠黏膜功能障碍有关。白藜芦醇通过调节自噬发挥抗炎作用。

目的：研究白藜芦醇对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎小鼠肠黏膜屏障完整性和抗炎的作用及机制。

方法：雄性 C57BL/6 小鼠分为四组：阴性对照组、DSS 模型组、DSS+白藜芦醇组和 DSS+5-氨基水杨酸组。通过疾病活动指数评估结肠炎的严重程度，通过酶联免疫吸附试验检测血清炎症细胞因子。苏木精和伊红染色，通过平均组织学评分评估黏膜损伤。免疫组织化学分析评估结肠组织中闭合蛋白和 ZO-1 的表达。此外，通过逆转录-聚合酶链反应和 Western blot 测定自噬相关基因的表达，并通过透射电子显微镜观察自噬体的形态。

结果：与 DSS 组相比，白藜芦醇治疗组 DSS 诱导的结肠炎小鼠的疾病活动指数评分降低了 1.72 倍，肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β的产生分别降低了 1.42、3.81 和 1.65 倍（<0.05）。DSS 模型组紧密连接蛋白 occludin 和 ZO-1 的表达降低，白藜芦醇治疗的结肠炎组表达增加。白藜芦醇还增加了 LC3B（与 DSS 组相比增加了 1.39 倍）和 Beclin-1（与 DSS 组相比增加了 1.49 倍）（<0.05），以及自噬体的数量，这意味着白藜芦醇可能通过增强自噬来减轻 DSS 诱导的 UC 小鼠的肠黏膜屏障功能障碍。

结论：白藜芦醇治疗降低了炎症因子的表达，增加了紧密连接蛋白的表达，缓解了 UC 肠黏膜屏障功能障碍；这种作用可能是通过增强肠上皮细胞中的自噬来实现的。