Exploring the Mechanism of LUO's Neiyi Prescription for the Treatment of Endometriosis Based on the HIF1A/EZH2/ANTXR2 Pathway
Objective To investigate the intervention effect and mechanism of LUO's Neiyi Prescription on the proliferation and angiogenesis of eutopic endometrium in rats with endometriosis(EMs)based on hypoxia-inducible factor 1A(HIF1A)/enhancer of zeste homolog 2(EZH2)/anthrax toxin receptor 2(ANTXR2)signaling pathway.Methods SD rats were randomly divided into sham operation group,model group,Danazol group(4.2 g·kg-1),low-dose LUO's Neiyi Prescription group and high-dose LUO's Neiyi Prescription group(15.74,31.48 g·kg-1),eight rats in each group.The rat model of EMs with qi stagnation and blood stasis syndrome was constructed by autologous endometrial transplantation combined with multi-factor intervention.Intragastric administration was given once a day for 28 consecutive days.The pathological changes of endometrial tissue were observed by HE staining.The expression levels of proliferating cell protein 67(Ki67)and platelet endothelial cell adhesion molecule 1(CD31)in endometrial tissue were detected by immunohistochemistry.The mRNA and protein expression levels of HIF1A,EZH2 and ANTXR2 in endometrial tissues were detected by qRT-PCR and Western Blot.The expression levels of YAP1,CD44 and β-catenin in endometrial tissues were detected by Western Blot.Results Compared with the sham operation group,the epithelial cells of the eutopic endometrium of the model group were thickened,the interstitial cells were arranged disorderly,and the inflammatory cells increased.The expression levels of Ki67 and CD31 in endometrial tissues were significantly increased(P＜0.01),the mRNA and protein expression levels of HIF1A and ANTXR2 were significantly increased(P＜0.01),while the mRNA and protein expression levels of EZH2 were significantly decreased(P＜0.01),and the protein expression levels of YAP1,CD44 and β-catenin were significantly increased(P＜0.01).Compared with the model group,the epithelial layer of the eutopic endometrial tissue of the rats in each administration group became thinner,the interstitial disorder and inflammatory infiltration were improved,and the levels of Ki67 and CD31 in the eutopic endometrial tissue were significantly decreased(P＜0.01).The mRNA and protein expression levels of HIF1A and ANTXR2 in the endometrium of rats in the Danazol group and the high-dose LUO's Neiyi Prescription group were significantly decreased(P＜0.05,P＜0.01),and the mRNA and protein expression levels of EZH2 were significantly increased(P＜0.05,P＜0.01).The protein expression levels of YAP1,CD44 and β-catenin in endometrial tissue of rats in each administration group were significantly decreased(P＜0.05,P＜0.01).Conclusion LUO's Neiyi Prescription can play a role in the treatment of EMs by inhibiting the proliferation and angiogenesis of eutopic endometrial cells,and its mechanism may be related to the inhibition of HIF1A/EZH2/ANTXR2 signaling pathway.
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