Xu Qinglei, Liu Mingzheng, Chao Xiaohuan, Zhang Chunlei, Yang Huan, Chen Jiahao, Zhao Chengxin, Zhou Bo
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Yantai Jinhai Pharmaceutical Co., Ltd., Yantai 265323, China.
Antioxidants (Basel). 2022 Oct 10;11(10):2002. doi: 10.3390/antiox11102002.
In this study, we evaluated the protective effects and potential mechanisms of acidifiers on intestinal epithelial cells exposure to oxidative stress (OS). IPEC-J2 cells were first pretreated with 5 × 10 acidifiers for 4 h before being exposed to the optimal dose of diquat to induce oxidative stress. The results showed that acidifiers attenuated diquat-induced oxidative stress, which manifests as the improvement of antioxidant capacity and the reduction in reactive oxygen species (ROS) accumulation. The acidifier treatment decreased cell permeability and enhanced intestinal epithelial barrier function through enhancing the expression of claudin-1 and occludin in diquat-induced cells. Moreover, acidifier treatment attenuated diquat-induced inflammatory responses, which was confirmed by the decreased secretion and gene expression of pro-inflammatory (TNF-α, IL-8) and upregulated anti-inflammatory factors (IL-10). In addition, acidifiers significantly reduced the diquat-induced gene and protein expression levels of COX-2, NF-κB, I-κB-β, ERK1/2, and JNK2, while they increased I-κB-α expression in IPEC-J2 cells. Furthermore, we discovered that acidifiers promoted epithelial cell proliferation (increased expression of and ) and inhibited apoptosis (decreased expression of , increased expression of ). Taken together, these results suggest that acidifiers are potent antioxidants that attenuate diquat-induced inflammation, apoptosis, and maintain cellular barrier integrity by regulating the NF-κB/MAPK/COX-2 signaling pathways.
在本研究中,我们评估了酸化剂对暴露于氧化应激(OS)的肠上皮细胞的保护作用及其潜在机制。IPEC-J2细胞在暴露于最佳剂量的敌草快以诱导氧化应激之前,先用5×10的酸化剂预处理4小时。结果表明,酸化剂减轻了敌草快诱导的氧化应激,表现为抗氧化能力的提高和活性氧(ROS)积累的减少。酸化剂处理通过增强敌草快诱导细胞中claudin-1和occludin的表达,降低了细胞通透性并增强了肠上皮屏障功能。此外,酸化剂处理减轻了敌草快诱导的炎症反应,这通过促炎因子(TNF-α、IL-8)分泌和基因表达的降低以及抗炎因子(IL-10)的上调得到证实。此外,酸化剂显著降低了敌草快诱导的IPEC-J2细胞中COX-2、NF-κB、I-κB-β、ERK1/2和JNK2的基因和蛋白表达水平,同时增加了I-κB-α的表达。此外,我们发现酸化剂促进上皮细胞增殖(和表达增加)并抑制细胞凋亡(表达降低,表达增加)。综上所述,这些结果表明,酸化剂是有效的抗氧化剂,可通过调节NF-κB/MAPK/COX-2信号通路减轻敌草快诱导的炎症、凋亡并维持细胞屏障完整性。