Study To Rabbit Endometrial Epithelial Cells α7nAChR Mediated Expression Of Inflammatory Factors

The complex physiological changes experienced by the female after production make the uterus easy to be infected by the pathogen and appear endometritis,endometritis decreases the conception rate and reproduction rate,even leads to infertility and elimination of the female animals.Among the prevention and treatment strategies for endometritis,antibiotics could enhance bacterial resistance,hormones affect the estrus cycle of female animals,then the development of new therapeutic targets for endometritis has become the focus of research.α7 nicotinic acetylcholine receptor is a key factor of the cholinergic anti-inflammatory pathway,which plays a role in regulating immune response and controlling inflammation.The purpose of this study was to elucidate the effect ofα7nAChR on the expression of inflammatory factors after lipopolysaccharides（LPS）stimulation of rabbit endometrial epithelial cells and the possible regulation mechanisms involved.The results showed that after 12 h of LPS stimulation,the contents of IL-1β,IL-6,IL-8,TNF-α,PGE₂ and PGF2αin rabbit endometrial epithelial cells were significantly up-regulated in cell culture supernatant.Nicotine,as an agonist,inhibited the contents of IL-1β,IL-6,IL-8,TNF-α,PGE₂ and PGF2αafter LPS stimulation,and this inhibition was inhibited by MLA,aα7nAChR specific inhibitor,and restored to a similar level compared to LPS stimulation group alone.The results of protein expression showed that LPS significantly down-regulated the expression levels of m PGES-1,AKR1C3,COX2 and the phosphorylation level of JAK2/STAT3 pathway.Compared with LPS-treated group,both nicotine and PNU282987could induce the enhancement of COX2 expression,and MLA could inhibit the promotion effect of PNU282987 on COX2 expression.PNU282987 could down-regulate the expression level of m PGES-1 after LPS stimulated cells,and MLA played a very significant role in promoting the expression of m PGES-1.Compared with LPS group,PNU282987 could down-regulate the phosphorylation of STAT3,and MLA down-regulate the phosphorylation of STAT3 after nicotine and LPS co-treatment.These results suggest that activation ofα7nAChR in rabbit endometrial epithelial cells can inhibit the secretion of inflammatory cytokines IL-1β,IL-6,IL-8,TNF-α,PGE₂and PGF2α,and the increased expression of COX2 mediated byα7nAChR may have a potential effect in this regulation process.However,the JAK2/STAT3 signaling pathway has no significantly direct influence on the main regulatory mechanisms involved in chronic infection of rabbit endometrial epithelial cells.