The Mechanism of Melatonin Inhibiting the Progression of Endometriosis Through NF-κB/NLRP3 Signaling Pathway
Objective:To investigate inhibitory effect of melatonin(MEL)on the progression of endometriosis(EMT),and its regulatory mechanism on nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization do-main-like receptors family pyrin domain containing 3(NLRP3)signaling pathway.Methods:EMT rats were estab-lished by subcutaneous implantation of autologous endometrium.Animal experimental models were divided into sham surgery group(Sham group,rats only underwent uterine segment cutting during the modeling process),and four experimental treatment groups,as follows:model group(EMT group,rats underwent subcutaneous implanta-tion of autologous endometrium),melatonin group(EMT +MEL group,rats were treated with50 mg/kg of MEL by gavage),and EMT +NF-κB signaling pathway activator phorbol ester(PMA)group(EMT +PMA group,rats were injected intraperitoneally with5 mg/kg PMA),EMT +MEL +PMA group(rats were treated by gavage with50 mg/kg MEL and intraperitoneal injection with 5 mg/kg PMA).The quality of endometriosis of rats,and the content of tumor necrosis factor α(TNF-α)and interleukin-6(IL-6)in the serum and peritoneal fluid in each group was detec-ted.Immunohistochemistry and immunofluorescence were used to detect the expression of myeloperoxi-dase(MPO)and vascular endothelial growth factor(VEGF).Western blot assay was used to detect the expression of NF-κB/NLRP3 signaling pathway in tissue samples.Results:Compared with Sham group,the proportion of es-trous cycle disorder,the quality of ectopic endometrium,the content of TNF-α and IL-6 in serum and peritoneal flu-id,the expression of MPO and VEGF,in EMT,EMT +MEL,EMT +PAM and EMT +MEL +PAM groups,the ex-pressions of NF-κB/NLRP3 signaling pathway were increased significantly(P<0.05).Compared with EMT group,the above indicators in the EMT +MEL group and EMT +MEL +PAM group decreased significantly,while the indicators in the EMT +PAM group increased significantly.Compared with the EMT +MEL group,the above indicators in the EMT + MEL + PAM group and EMT + PAM group were significantly increased.The differences were all statistically significant(P<0.05).Conclusions:MEL could significantly inhibit the inflammatory response and the progression of endometriosis,which may be achieved by inhibiting the activation of NF-κB/NLRP3 signa-ling pathway.
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