The Protective Effects And Mechanisms Of Sodium Butyrate On Blood-milk Barrier In A Mouse Model Of Mastitis Induced By LPS

Mastitis is the inflammation of mammary glands,often caused by pathogenic microorganisms and physicochemical factors.Mastitis decreases milk production and reduces milk quality,which brings huge economic losses of dairy farming industry.The blood-milk barrier formed by alveolar tight junctions provides important protection for milk integrity and the health of pups.There is some evidence that mastitis leads to losses in blood-milk barrier function are directly contributing to tissue damage of mammary glands.It is suggests that maintaining blood-milk barrier function benefits inflammation.Short-chain fatty acids butyrate has anti-inflammatory,antioxidant and anti-arthritic activities.Recent evidence suggests that sodium butyrate(SB)has exhibited protective activity on disruption of blood-brain barrier and gut barrier.However,the protective effects of SB on the blood-milk barrier and its underlying mechanism remain ill-defined.Here,the protective effects and the molecular basis of action of SB were investigated by assessing alterations in the integrity of the blood-milk barrier and the inflammatory response to LPS.Firstly,we observed the effects of SB on LPS-induced mastitis in mice.The results show that SB decreased LPS-induced disruption in mammary tissues,infiltration of inflammatory cells,MPO activity and the levels of TNF-?,IL-1? and IL-6.Our studies have shown that SB treatment significantly ameliorated mammary tissue injury in LPS-induced mastitis.Secondly,the leakage of FITC-albumin from the interstitial side into the alveolar lumen was observed,following treatment with LPS.Correspondingly,treatment of the mammary glands with SB caused reduced this LPS-induced leakage of FITC-albumin into the alveolar lumen.As recognised,the structure and functional integrity of tight junctions are maintained by the tight junction proteins,Claudins and Occludin.In our experiments,we showed that SB up-regulated the expression of these tight junction-associated proteins.All the results suggest that SB exerts protective effects on the blood-milk barrier in LPS-induced mastitis.Finally,we established LPS-stimulated mouse mammary epithelial cells(m MECs)model to further confirm the protective mechanisms of SB on the blood-milk barrier.Studies in vitro revealed that SB has no effect on viability of the m MECs.SB inhibited LPS-induced inflammatory response by inhibition of the NF-?B signaling pathway and histone deacetylases(HDACs)in LPS-stimulated m MECs.In our model,SB protected against LPS-induced mastitis by preserving blood-milk barrier function and depressing pro-inflammatory responses,suggesting the potential use of SB as a feed additive to protect blood-milk barrier function in mastitis.