Palmitic Acid And β-hydroxybutyrate Induce Inflammatory Responses In Bovine Endometrial Cells By Activating Oxidative Stress-mediated NF-κB Signaling

[Background] Palmitic acid(PA)and β-hydroxybutyrate(BHBA)are important inducers of inflammatory responses in some metabolic diseases.PA is a main component of saturated fatty acids among non-esterified fatty acids(NEFA).Both PA and BHBA have higher concentrations in the blood of ketosis cattle.Hyperketonemia and hyper-free fatty acidemia is closely related to the occurrence of inflammatory diseases(such as mastitis and endometritis)in dairy cows.[Objective] The aim of this study was to investigate whether high levels of PA and BHBA can activate the oxidative stress-mediated NF-κB signaling pathway to promote the synthesis of inflammatory factors in bovine endometrial cells.It provides valuable information for understanding the pathogenic relationship between nutritional metabolic diseases and uterine inflammation.[Methods] In this study,using the commercial kits,ELISA,RT-PCR and Western blot evaluated the oxidative stress,pro-inflammatory factors and NF-κB pathway in cultured BEND cells treated with different concentrations of PA,BHBA,pyrrolidinedithiocarbamate(PDTC,an NF-κB pathway inhibitor)and N-acetylcysteine(NAC,antioxidant).[Results] It was found that the content of malondialdehyde(MDA)in the treated cells was significantly higher,the content of glutathione(GSH)was lower,and the activity of the antioxidant system in the cells was lower,including glutathione peroxidase(GSH-PX),superoxide dismutase(SOD),catalase(CAT)and total antioxidant capacity(T-AOC).Oxidative stress induced by PA and BHBA activates the NF-κB signaling pathway and up-regulates the release of pro-inflammatory factors.Activation of NF-κB-mediated inflammatory responses induced by PA and BHBA was inhibited when PDTC and NAC were added.[Conclusion] Palmitic acid and β-hydroxybutyrate activate NF-κB signaling pathway mediated by oxidative stress,thereby up-regulating the expression and release of the inflammatory factors IL-6,IL-8 and TNF-α,resulting in an enhanced inflammatory response inflammatory damage of bovine endometrial cells.