首页|基于P53/P21信号通路探讨培元益肾安胎方对高龄复发性流产小鼠细胞衰老及蜕膜化的影响

基于P53/P21信号通路探讨培元益肾安胎方对高龄复发性流产小鼠细胞衰老及蜕膜化的影响

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目的 基于P53/P21信号通路观察培元益肾安胎方调控高龄复发性流产(RSA)小鼠细胞衰老及蜕膜化过程,探讨其治疗RSA的作用机制。方法 将8~9月龄CBA/J雌鼠随机分为高龄模型组(生理盐水0。3mL/d)、中药组(18。72 g/kg)和地屈孕酮组(2。6mg/kg),6~8周龄CBA/J雌鼠为育龄空白组(生理盐水0。3mL/d),每组5只,分别予相应药液灌胃2周后,将育龄空白组小鼠与BALB/c雄鼠合笼,其余各组与DBA/2雄鼠合笼,确认见栓后继续灌胃至妊娠第9日取材。观察小鼠胚胎丢失率,HE染色观察子宫蜕膜形态,免疫组化法检测蜕膜组织衰老相关蛋白P16INK4a定位及表达,RT-PCR及Western blot检测蜕膜组织P53、P21、胰岛素样生长因子结合蛋白1(IGFBP-1)、泌乳素(PRL)mRNA及蛋白表达。结果 与育龄空白组比较,高龄模型组小鼠胚胎丢失率显著升高(P<0。05),子宫内膜形态不规则,细胞呈空泡状且腺体及血管数量减少,蜕膜组织P16INK4a表达显著升高(P<0。05),P53、P21 mRNA及蛋白表达显著升高(P<0。05),IGFBP-1、PRLmRNA及蛋白表达显著下降(P<0。05);与高龄模型组比较,中药组和地屈孕酮组小鼠胚胎丢失率有下降趋势,蜕膜组织细胞排列较整齐,血管和腺体数量增加,蜕膜组织P16INK4a表达显著降低(P<0。05),P53、P21 mRNA及蛋白表达显著降低(P<0。05),IGFBP-1、PRLmRNA及蛋白表达显著升高(P<0。05)。结论 培元益肾安胎方可能通过调控P53/P21信号通路改善高龄RSA模型小鼠子宫内膜基质细胞衰老状态,促进蜕膜化进程,从而发挥保胎作用。
Effects of Peiyuan Yishen Antai Decoction on Cell Senescence and Decidualization of Aged Mice with Recurrent Spontaneous Abortion Based on P53/P21 Signaling Pathway
Objective To explore the effects of Peiyuan Yishen Antai Decoction on cell senescence and decidualization of aged mice with recurrent spontaneous abortion(RSA)based on P53/P21 signaling pathway;To discuss its mechanism in the treatment of RSA.Methods 8-9 month old CBA/J female mice were randomly divided into aging model group(normal saline 0.3 mL/d),Chinese materia medica group(18.72 g/kg)and dydrogesterone group(2.6 mg/kg).6-8 week old CBA/J female mice were assigned to a reproductive age blank group(normal saline 0.3 mL/d),with five mice in each group.After administering the corresponding solutions by gavage for 2 weeks,the reproductive age blank group mice were housed in cages with BALB/c male mice,while the remaining groups were housed in cages with DBA/2 male mice.After confirming the presence of vaginal plug,gavage was continued until the 9th day of pregnancy for sampling.Mice embryo loss rate was observed,HE staining was used to observe the morphology of uterine decidua,immunohistochemistry was used to detect the localization and expression of aging related protein Pi6INK4a in decidua tissue,RT-PCR and Western blot were used to detect the mRNA and protein expressions of P53,P21,insulin-like growth factor binding protein 1(IGFBP-1)and prolactin(PRL)in decidual tissue.Results Compared with the reproductive age blank group,the embryo loss rate of the aging model group significantly increased(P<0.05),the irregular endometrial cells were vacuolated,the number of glands and blood vessels was reduced,the expression of P16INK4a in decidual tissue significantly increased(P<0.05),and the expressions of P53,P21 mRNA and protein significantly increased(P<0.05),the mRNA and protein expressions of IGFBP-1 and PRL significantly decreased(P<0.05).Compared with the aging model group,the Chinese materia medica group and the dydrogesterone group showed an decreasing trend in embryo loss rate in mice,the arrangement of cells in the decidua tissue was relatively neat,and the number of blood vessels and glands increased,the expression of P16INK4a in decidua tissue was significantly decreased(P<0.05),the mRNA and protein expressions of P53 and P21 were significantly decreased(P<0.05),while the mRNA and protein expressions of IGFBP-1 and PRL significantly increased(P<0.05).Conclusion Peiyuan Yishen Antai Decoction can improve the aging status of endometrial stromal cells in aged RSA model mice by regulating the P53/P21 signaling pathway,promote decidualization process,and thus exert a protective effect on pregnancy.

agedrecurrent spontaneous abortionPeiyuan Yishen Antai Decoctiondecidualizationcell senescencemice

舒畅、刘雁峰、闫菲、邓楠、金凡惠、郭霖霖、徐子涵

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北京中医药大学东直门医院,北京 100700

北京中医药大学,北京 100029

高龄 复发性流产 培元益肾安胎方 蜕膜化 细胞衰老 小鼠

2025

中国中医药信息杂志
中国中医科学院中医药信息研究所

中国中医药信息杂志

影响因子:0.889
ISSN:1005-5304
年,卷(期):2025.32(1)