LPS challenge increased intestinal permeability disruptedmitochondrial function and triggered mitophagy of piglets

摘要

Here we investigated the influence of LPS-induced gut injury on antioxidanthomeostasis, mitochondrial (mt) function and the level of mitophagy in piglets.The results showed that LPS-induced intestinal injury decreased thetransepithelial electrical resistance, increased the paracellular permeabilityof F1TC dextran 4 kDa, and decreased the expression of claudin-1, occludin andzonula occludens-1 in the jejunum compared with the control group. LPS decreasedthe activities of superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px), and increased the content of malondialdehyde in the jejunum.Meanwhile, the expression of SOD-related genes ( , ) and GSH-Px-related genes ( , ) declined in LPS-challenged pigs compared with thecontrol. LPS also increased TNF-α, IL-6, IL-8 and IL-1β mRNA expression. LPSinduced mt dysfunction, as demonstrated by increased reactive oxygen speciesproduction and decreased membrane potential of intestinal mitochondria,intestinal content of mt DNA and activities of the intestinal mt respiratorychain. Furthermore, LPS induced an increase in expression of mitophagy relatedproteins, PTEN-induced putative kinase (PINK1) and Parkin in the intestinalmitochondria, as well as an enhancement of the ratio of light chain 3-II(LC3-II) to LC3-I content in the jejunal mucosa. These results suggested thatLPS-induced intestinal injury accompanied by disrupted antioxidant homeostasis,caused mt dysfunction and triggered mitophagy.