Mechanism study on the regulation of SIRT1-FoxO1 mediated cellular autophagy in the treatment of endometriosis by Bushen Wenyang Huayu Recipe
Objective:To explore the mechanism of SIRT1 FoxO1 mediated autophagy in the development of endometriosis(EMs),as well as the therapeutic effect and possible mechanism of Bushen Wenyang Huayu Recipe in the treatment of EMs.Methods:12Z cells were divided into CON group,DMSO group(+DMSO of the same volume),and EX527 group(+SIRT1 inhibitor).The migration ability of each group of cells was detected using scratch assay,and the invasion ability of cells was detected using Transwell cell assay.After collection,the localization and content expression of SIRT1,FoxOl,and autophagy related factor proteins were detected using immunofluorescence and Western Blot,respectively.100 experimental rats were randomly divided into sham surgery group,model group,traditional Chinese medicine(TCM)group,TCM+EX527 group,and EX527 group.After successful modeling of EMs,the TCM group and the TCM+EX527 group were given the Bushen Wenyang Huayu Recipe by gavage,while the sham operation group,model group,and EX527 group were gavaged with the same volume of pure water;The TCM+EX527 group and EX527 group were given intraperitoneal injection of EX527 solvent,while the other groups were given intraperitoneal injection of the same volume of physiological saline for 3 consecutive weeks.Immunohistochemistry and Western Blot were used to detect the localization and content expression of SIRT1,FoxO1,and autophagy related factors,respectively.Results:In cell experiments,compared with the CON or DMSO groups,the EX527 group showed a significant increase in migration and invasion ability,a significant decrease in SIRT1 levels(P＜0.05),and a significant increase in FoxO1 and autophagy related factors levels(P＜0.05,P＜0.01).In animal experiments,compared with the sham surgery group,the SIRT1 levels in the model group and EX527 group were significantly reduced(P＜0.05),while the levels of FoxO1 and autophagy related factors were significantly increased(P＜0.01).The SIRT1 levels in the TCM group and the TCM+EX527 group were significantly increased(P＜0.01),while the levels of FoxO1 and autophagy related factors were significantly decreased(P＜0.05,P＜0.01).Conclusions:SIRT1 mediates FoxOl to negatively regulate cell autophagy levels.The Bushen Wenyang Huayu Recipe may upregulate SIRT1,inhibit FoxO1 mediated autophagy,and thus have a therapeutic effect on EMs.
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