Guangdong Provincial Key Laboratory of Animal Nutritional Control , 483 Wushan Road, Tianhe District , Guangzhou , Guangdong 510642 , China.
College of Animal Science , South China Agricultural University , 483 Wushan Road, Tianhe District , Guangzhou , Guangdong 510642 , China.
J Agric Food Chem. 2019 Aug 28;67(34):9477-9491. doi: 10.1021/acs.jafc.9b02925. Epub 2019 Aug 20.
Lipopolysaccharide (LPS) is a bacterial endotoxin that induces intestine inflammation. Milk exosomes improve the intestine and immune system development of newborns. This study aims to establish the protective mechanisms of porcine milk exosomes on the attenuation of LPS-induced intestinal inflammation and apoptosis. In vivo, exosomes prevented LPS-induced intestine damage and inhibited ( < 0.05) LPS-induced inflammation. In vitro, exosomes inhibited ( < 0.05) LPS-induced intestinal epithelial cells apoptosis (23% ± 0.4% to 12% ± 0.2%). Porcine milk exosomes also decreased ( < 0.05) the LPS-induced TLR4/NF-κB signaling pathway activation. Furthermore, exosome miR-4334 and miR-219 reduced ( < 0.05) LPS-induced inflammation through the NF-κB pathway and miR-338 inhibited ( < 0.05) the LPS-induced apoptosis via the p53 pathway. Cotransfection with these three miRNAs more effectively prevented ( < 0.05) LPS-induced cell apoptosis than these miRNAs individual transfection. The apoptosis percentage in the group cotransfected with the three miRNAs (14% ± 0.4%) was lower ( < 0.05) than that in the NC miRNA group (28% ± 0.5%), and also lower than that in each individual miRNA group. In conclusion, porcine milk exosomes protect the intestine epithelial cells against LPS-induced injury by inhibiting cell inflammation and protecting against apoptosis through the action of exosome miRNAs. The presented results suggest that the physiological amounts of miRNAs-enriched exosomes addition to infant formula could be used as a novel preventative measure for necrotizing enterocolitis.
脂多糖（LPS）是一种细菌内毒素，可诱导肠道炎症。牛奶外泌体可改善新生儿的肠道和免疫系统发育。本研究旨在确定猪乳外泌体对减轻 LPS 诱导的肠道炎症和细胞凋亡的保护机制。在体内，外泌体可预防 LPS 诱导的肠道损伤，并抑制 LPS 诱导的炎症（<0.05）。在体外，外泌体抑制 LPS 诱导的肠上皮细胞凋亡（23%±0.4%至 12%±0.2%）。猪乳外泌体还降低了 LPS 诱导的 TLR4/NF-κB 信号通路的激活。此外，外泌体 miR-4334 和 miR-219 通过 NF-κB 通路降低 LPS 诱导的炎症，miR-338 通过 p53 通路抑制 LPS 诱导的细胞凋亡。这三种 miRNA 的共转染比单独转染更有效地预防 LPS 诱导的细胞凋亡（<0.05）。共转染这三种 miRNA 的细胞凋亡百分比（14%±0.4%）低于阴性对照 miRNA 组（28%±0.5%），也低于单独转染每种 miRNA 的细胞凋亡百分比。总之，猪乳外泌体通过抑制细胞炎症和防止细胞凋亡来保护肠上皮细胞免受 LPS 诱导的损伤，其作用机制与外泌体 miRNA 有关。这些结果表明，在婴儿配方奶粉中添加富含生理浓度 miRNA 的外泌体可能成为防治坏死性小肠结肠炎的一种新的预防措施。
