Kang Jian, Zhou Yanhong, Zhu Chunyang, Ren Tian, Zhang Yong, Xiao Longfei, Fang Binghu
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510630, China.
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Toxics. 2022 May 27;10(6):285. doi: 10.3390/toxics10060285.
Inflammation leads to porcine tight junction disruption of small intestinal epithelial cells, resulting in intestinal dysfunction. Herein, we established lipopolysaccharide (LPS)-induced in-vivo and in-vitro inflammatory models. The results revealed that LPS induced tight junction disruption in IPEC-J2 cells by downregulating tight-junction-related protein zonula occludens-1 (ZO-1), occludin and claudin-1 expression, while ginsenoside Rg1 rescued such inhibition and abrogated the upregulated expression of phosphorylation p38 MAPK. The p38 MAPK inhibitor (SB203580) showed a similar effect with Rg1 and attenuated the LPS-induced inhibition of ZO-1, occludin and claudin-1 expression, which is consistent with the reduced expression of inflammasome and . Furthermore, the specific inhibitors of and result in increased expression of tight-junction-related protein, demonstrating that p38 MAPK signaling was associated with Rg1 suppression of tight junction disruption. Besides, LPS treatment decreased the expression of ZO-1, occludin and claudin-1 through p38 MAPK signaling, and caused abnormal morphological changes in murine ileum. Meanwhile, Rg1 attenuated the decreased expression of ZO-1, occludin and claudin-1 and partially alleviated LPS-induced morphological changes in murine ileum. In summary, these findings characterized a novel mechanism by which Rg1 alleviates LPS-induced intestinal tight junction disruption by inhibiting the p38 MAPK-mediated inflammasome pathway.
炎症会导致猪小肠上皮细胞紧密连接破坏，进而引起肠道功能障碍。在此，我们建立了脂多糖（LPS）诱导的体内和体外炎症模型。结果显示，LPS通过下调紧密连接相关蛋白闭合蛋白1（ZO-1）、闭合蛋白（occludin）和紧密连接蛋白1（claudin-1）的表达，诱导IPEC-J2细胞紧密连接破坏，而人参皂苷Rg1可挽救这种抑制作用，并消除磷酸化p38丝裂原活化蛋白激酶（MAPK）的上调表达。p38 MAPK抑制剂（SB203580）显示出与Rg1相似的作用，并减弱了LPS诱导的对ZO-1、occludin和claudin-1表达的抑制，这与炎性小体表达的降低一致。此外，[具体蛋白名称1]和[具体蛋白名称2]的特异性抑制剂导致紧密连接相关蛋白表达增加，表明p38 MAPK信号通路与Rg1对紧密连接破坏的抑制作用相关。此外，LPS处理通过p38 MAPK信号通路降低ZO-1、occludin和claudin-1的表达，并导致小鼠回肠形态异常改变。同时，Rg1减弱了ZO-1、occludin和claudin-1表达的降低，并部分缓解了LPS诱导的小鼠回肠形态改变。总之，这些发现揭示了一种新机制，即Rg1通过抑制p38 MAPK介导的炎性小体途径减轻LPS诱导的肠道紧密连接破坏。
