Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Food Funct. 2020 Apr 30;11(4):3741-3748. doi: 10.1039/d0fo00030b.
Impairment of the intestinal barrier often occurs in inflammatory bowel diseases, and pro-inflammatory factors play a vital role in the pathogenesis of intestinal diseases. In our study, the potential protective effects of Lycium barbarum polysaccharides (LBP) against intestinal barrier dysfunction evoked by pro-inflammatory factors and its anti-inflammatory effects were investigated. Caco-2 cells were stimulated with or without tumor necrosis factor (TNF)-α in the presence or absence of LBP. Our findings showed that LBP assuaged the increase of paracellular permeability and the decrease of transepithelial electrical resistance (TER) in Caco-2 cells. In addition, LBP also prevented the secretion of pro-inflammatory markers (IL-8, IL-6, ICAM-1 and MCP-1) in TNF-α-challenged Caco-2 cells. Moreover, LBP inhibited the overexpression of tight junction (TJ) proteins (claudin-1, ZO-3, and occludin) and the increase of MLCK, pMLC, p-IκBα and NFκBp65 protein expression evoked by TNF-α was suppressed by LBP pre-incubation. This finding indicated that LBP improve TNF-α-evoked intestinal barrier dysfunction via suppressing the MLCK-MLC signaling pathway mediated by NFκB.
肠屏障功能障碍在炎症性肠病中经常发生，促炎因子在肠道疾病的发病机制中起着至关重要的作用。在本研究中，我们研究了枸杞多糖（LBP）对促炎因子诱导的肠屏障功能障碍的潜在保护作用及其抗炎作用。用或不用肿瘤坏死因子（TNF）-α刺激 Caco-2 细胞，并在存在或不存在 LBP 的情况下进行刺激。我们的研究结果表明，LBP 减轻了 TNF-α 刺激的 Caco-2 细胞中细胞旁通透性的增加和跨上皮电阻（TER）的降低。此外，LBP 还可以防止 TNF-α 刺激的 Caco-2 细胞中促炎标志物（IL-8、IL-6、ICAM-1 和 MCP-1）的分泌。此外，LBP 抑制了 TNF-α 诱导的紧密连接（TJ）蛋白（claudin-1、ZO-3 和 occludin）的过度表达，以及肌球蛋白轻链激酶（MLCK）、磷酸化肌球蛋白轻链（p-MLC）、磷酸化核因子κB 抑制蛋白α（p-IκBα）和 NFκBp65 蛋白表达的增加，LBP 预先孵育抑制了这些蛋白的表达。这一发现表明，LBP 通过抑制 NFκB 介导的肌球蛋白轻链激酶（MLCK）-肌球蛋白（MLC）信号通路来改善 TNF-α 诱导的肠屏障功能障碍。
