Bushen Wenyang Huayu Decoction inhibits autophagy by regulating the SIRT1-FoXO-1 pathway in endometriosis rats

补肾温阳化瘀汤通过调控SIRT1-FoXO-1通路抑制子宫内膜异位症大鼠自噬

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作者:Ying Li, Mingli An, Xinping Fu, Xin Meng, Yiming Ma, Huimin Liu, Qingxue Li, Huazhou Xu, Jingwei Chen

Aim of the study

We evaluated the expression and role of the SIRT1-FoxO-1 pathway and autophagy levels in EMs rats. The therapeutic effects and potential therapeutic mechanisms of BWHD were also investigated.

Conclusions

BWHD inhibits autophagy by up-regulating SIRT1 and down-regulating FoXO-1 expression in EMs via the SIRT1-FoXO-1 signaling pathway. Therefore, it is a potential treatment for EMs.

Methods

Twenty rats were randomized into the sham group and eighty rats were used for model establishment by autologous transplantation. After successful modeling, they were randomized into the model, BWHD, EX527+BWHD and EX527 groups, with 20 rats in each group. All rats were intragastrically administered with for 3 weeks. Localization of Sirtuin 1 (SIRT1), Forkhead boxO-1 (FoXO-1), Beclin-1, autophagy-related 5 (Atg5) and autophagy-related 7 (Atg7) was determined by immunohistochemical staining. The expression of the above proteins was determined by Western blot and their messenger RNA (mRNA) levels were detected by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).

Results

The protein and mRNA expressions of FoXO-1, Beclin-1, Atg5 and Atg7 in the model group were markedly increased, while that of SIRT1 was markedly decreased relative to the sham group (p < 0.05 and p<0.01, respectively). Results showed that the protein and mRNA expressions of FoXO-1, Beclin-1, Atg5 and Atg7 in eutopic and ectopic endometrium of BWHD group were lower, while SIRT1 expression was higher than in the model group (p < 0.05 and p<0.01, respectively). Furthermore, protein and mRNA expression levels of FoXO-1, Beclin-1, Atg5 and Atg7 in eutopic and ectopic endometrium of EX527 group were higher, while SIRT1 level was significantly lower than in the model group (p < 0.05 and p < 0.01, respectively). The EX527-induced changes in protein and mRNA expressions were reversed in the EX527+BWHD group (p < 0.05 and p < 0.01, respectively). Conclusions: BWHD inhibits autophagy by up-regulating SIRT1 and down-regulating FoXO-1 expression in EMs via the SIRT1-FoXO-1 signaling pathway. Therefore, it is a potential treatment for EMs.

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