Salvianolic Acid B Regulates Trophoblast-Macrophage Interaction in Recurrent Spontaneous Abortion via RORA/SENP1 Pathway
Objective To investigate the effect of salvianolic acid B(SalB)on regulating the interaction between trophoblast cells and macrophages via the receptor related orphan receptor alpha(RORA)/sentrin specific peptidase 1(SENP1)pathway,and to explore its underlying mechanism in recurrent spontaneous abortion(RSA).Methods HTR-8/SVneo cells were treated with SalB,oe-RORA,and oe-SENP1 transfection vectors.A Transwell co-culture system was used to facilitate communication be-tween HTR-8/SVneo cells and M1 macrophages.CCK-8 assay was performed to assess HTR-8/SVneo cell prolifera-tion.Transwell assay was used to detect the invasive capacity of HTR-8/SVneo cells.TUNEL staining was applied to evaluate apoptosis,qRT-PCR was employed to quantify the levels of polarization markers CD86 and CD163 in HTR-8/SVneo cells.Western blot was conducted to determine the expression of RORA and SENP1.An RSA mouse model was established to explore the in vivo effects of SalB on RSA.Results Compared with the control group,HTR-8/SVneo cell proliferation and in-vasion were promoted in a dose-dependent manner in SalB group,while apoptosis was inhibited.M1 macrophage co-culture in-creased the levels of M1 macrophage polarization markers in HTR-8/SVneo cells and suppressed cell growth,whereas SalB treatment significantly decreased CD86 levels,increased CD163 levels,and induced HTR-8/SVneo cell proliferation and inva-sion.SalB intervention notably inhibited RORA expression compared to the control group,while RORA overexpression signifi-cantly suppressed HTR-8/SVneo cell proliferation and invasion,and significantly promoted apoptosis rates.Compared to the HTR-8/SVneo+M1 group,RORA overexpression significantly inhibited SENP1 protein levels,while SENP1 overexpression reversed the effects of RORA on HTR-8/SVneo cells.In vivo experiments showed that SalB treatment significantly reduced embryo resorption and abortion rates in RSA mice.Conclusion SalB regulates the interaction between trophoblast cells and macrophages by inhibiting RORA and activating SENP1,thereby inhibiting RSA progression.
salvianolic acid Breceptor related orphan receptor alphamacrophagerecurrent spontaneous abortion
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