关键词: 原儿茶酸, 溃疡性结肠炎, Toll样受体4, 核因子-κB, 肠屏障功能

Abstract: Objective To investigate the effect of protocatechuic acid (PCA) on Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signal pathway in rats with ulcerative colitis (UC). Methods After modeling, rats were divided into control group, model group (5% trinitrobenzene sulfonic acid (TNBS) induction), low (L-PCA), middle (M-PCA), high (H-PCA) dose protocatechuic acid group (rats were given with PCA at doses of 20, 40 and 80 mg/kg respectively), and intervention model group (LPS, rats were given with PCA at doses of 80 mg/kg and 0.8 mg/kg LPS solution intraperitoneally), and 12 rats in each group were given the drug continuously for 14 days. After treatment, rats were evaluated by disease activity index (DAI), and the morphology and apoptosis of colon were observed by hematoxylin eosin (HE) staining and TUNEL staining. The protein levels of Occludin, Zona occludens 1 (ZO-1), claudin-1, Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-10, TLR4 and p-p65/p65 in colon were detected by Western blotting. The expression of TLR4 protein in colon was detected by immunohistochemical staining. Results Compared with control group, the colon of model group rat showed obvious injury, DAI score and positive rate of TUNEL were increased (P＜0.05), the relative protein expression of TNF-α, IL-1β, TLR4 and p-p65 were increased (P＜0.05), the relative protein expression of Occludin, ZO-1, claudin-1 and IL-10 were decreased (P＜0.05). Compared with model group, colonic injury was alleviated in L-PCA, M-PCA and H-PCA groups, DAI score and positive rate of TUNEL were decreased (P＜0.05), the relative protein expression of TNF-α, IL-1β, TLR4 and p-p65 were decreased (P＜0.05), the relative protein expression of Occludin, ZO-1, claudin-1 and IL-10 were increased (P＜0.05). Compared with H-PCA group, colon injury was aggravated in LPS group, DAI score and positive rate of TUNEL were increased (P＜0.05), the relative protein expression of TNF-α, IL-1β, TLR4 and p-p65 was increased (P＜0.05), the relative protein expression of Occludin, ZO-1, claudin-1 and IL-10 was decreased (P＜0.05). Conclusions Protocatechuic acid can alleviate TNBS-induced colon injury in UC rats, improve intestinal barrier function, and inhibit colon inflammatory response, the mechanism of which is related to the activation of TLR4/NF-κB signaling pathway.

Key words: protocatechuic acid, ulcerative colitis, Toll-like receptor 4, NF-κB, intestinal barrier function