四君子汤通过 NF-κB 通路减轻 2,4,6-三硝基苯磺酸（TNBS）诱导的大鼠结肠炎和改善 Caco2 细胞中 TNBS 诱导的闭合蛋白-2 损伤。
Sijunzi Decoction attenuates 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats and ameliorates TNBS-induced claudin-2 damage via NF-κB pathway in Caco2 cells.
机构信息
The Second Clinical College, GuangzhouUniversity of Chinese Medicine, Guangzhou, 510000, China.
Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510000, China.
出版信息
BMC Complement Altern Med. 2017 Jan 10;17(1):35. doi: 10.1186/s12906-016-1549-3.
BACKGROUND
SijunziDecoction (SJZD) is a traditional Chinese medicine prescription used to treat the diseases of gastrointestinal tract since ancient times. The objective of this study was to investigate the protective effects of SJZD on TNBS-induced colitis in rats and TNBS-damaged Caco2 cells.
METHODS
The rat colitis model was induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). SJZD (2.8 5.6, 11.2 g/kg) or salazosulfapyridine (SASP) (0.4 g/kg) was administrated orally in rats for 7 days. DAI, pathological scores and the expression of claudin-2 were evaluated. Then we explored the effect and mechanism of SijunziDecoction Serum (SJZDS) onTNBS-damaged Caco2 cells to figure out intestinal barrier protective effect and mechanism of SJZD.
RESULTS
SJZD significantly ameliorated the severity of TNBS-induced colitis and downregulated the level of claudin-2 in colonic tissues. SJZDS promoted proliferation and inhibited apoptosis ofTNBS-damaged Caco2 cells. In Caco2 cell monolayers, we provided mechanistic evidence that SJZDS-induced increased TEER and decreased permeability after TNBS damage, which were mediated through claudin-2 and NF-κB pathway, including the upregulation of claudin-2, decreased activity of NF-κB p65, reduced level of NF-κB p65 and MLCK.
CONCLUSIONS
Our results indicated that SJZD possesses protective effect of intestinal barrier towards TNBS-induced colitis in rats and TNBS-damaged Caco2 cells in vitro. SJZDis a potential protective agent of intestinal barrier that deserves further investigation.
背景
四君子汤（SJZD）是一种传统的中药方剂，自古以来就用于治疗胃肠道疾病。本研究旨在探讨 SJZD 对大鼠 TNBS 诱导的结肠炎和 TNBS 损伤的 Caco2 细胞的保护作用。
方法
采用 2,4,6-三硝基苯磺酸（TNBS）诱导大鼠结肠炎模型。SJZD（2.8、5.6、11.2g/kg）或柳氮磺胺吡啶（SASP）（0.4g/kg）灌胃给药，连续 7d。评估 DAI、病理评分和紧密连接蛋白-2 的表达。然后，我们探讨了 SijunziDecoction 血清（SJZDS）对 TNBS 损伤的 Caco2 细胞的作用和机制，以阐明 SJZD 的肠道屏障保护作用及其机制。
结果
SJZD 显著改善了 TNBS 诱导的结肠炎的严重程度，并下调了结肠组织中紧密连接蛋白-2 的水平。SJZDS 促进了 TNBS 损伤的 Caco2 细胞的增殖，抑制了其凋亡。在 Caco2 细胞单层中，我们提供了机制证据表明，SJZDS 诱导的 TEER 增加和 TNBS 损伤后通透性降低是通过紧密连接蛋白-2 和 NF-κB 途径介导的，包括紧密连接蛋白-2 的上调、NF-κB p65 活性降低、NF-κB p65 和 MLCK 水平降低。
结论
我们的结果表明，SJZD 对大鼠 TNBS 诱导的结肠炎和体外 TNBS 损伤的 Caco2 细胞具有肠道屏障保护作用。SJZD 是一种有潜力的肠道屏障保护剂，值得进一步研究。
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