Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy

白藜芦醇通过增强自噬减轻葡聚糖硫酸钠诱导的结肠炎小鼠肠黏膜屏障功能障碍

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作者:Hang-Hai Pan, Xin-Xin Zhou, Ying-Yu Ma, Wen-Sheng Pan, Fei Zhao, Mo-Sang Yu, Jing-Quan Liu

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.

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.

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.

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 (P < 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) (P < 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.

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