基于VEGF/Hippo/YAP通路探讨补肾安胎合剂对复发性流产小鼠母胎界面血管新生的影响  

Effects of Bushen Antai Mixture on Maternal and Foetal Interface Angiogenesis in Recurrent Spontaneous Abortion Mice Based on the VEGF/Hippo/YAP Pathway

作　　者：李哲 梁程程 储海静 胡恒[1] 于静 储继军[2] LI Zhe;LIANG Chengcheng;CHU Haijing;HU Heng;YU Jing;CHU Jijun(Anhui University of Chinese Medicine,Hefei 230012,China;The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China)

机构地区：[1]安徽中医药大学,安徽合肥230012 [2]安徽中医药大学第一附属医院,安徽合肥230031

出　　处：《中国中医药信息杂志》2025年第4期107-112,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：安徽省高等学校科学研究重点项目(2023AH050853);全国名老中医药专家传承工作室建设项目(2022年);安徽省中药复方重点实验室(2024年)。

摘　　要：目的观察补肾安胎合剂对复发性流产(RSA)小鼠母胎界面血管新生的影响,基于VEGF/Hippo/YAP通路探讨其治疗RSA的作用机制。方法采用Clark经典造模方法构建RSA小鼠模型及正常妊娠小鼠。将RSA模型小鼠随机分为模型组、黄体酮组及补肾安胎合剂低、中、高剂量组,正常妊娠小鼠作为正常组,每组10只。妊娠第1日开始,各给药组分别予相应药物灌胃15 d。计算小鼠胚胎吸收率,HE染色观察蜕膜组织形态,实时荧光定量PCR、Western blot分别检测蜕膜组织血管内皮生长因子(VEGF)及Hippo/YAP通路相关分子mRNA和蛋白表达。结果与正常组比较,模型组小鼠胚胎吸收率明显升高(P<0.01),蜕膜组织细胞排列紊乱,水肿变性,部分细胞核消失,血管密度减少,蜕膜组织VEGF、Yes相关蛋白(YAP)、大肿瘤抑制因子(LATS)1、LATS2 mRNA表达明显降低(P<0.01),VEGF蛋白表达明显降低(P<0.01),p-YAP/YAP、p-LATS/LATS蛋白表达明显升高(P<0.01);与模型组比较,补肾安胎合剂各剂量组小鼠胚胎吸收率明显降低(P<0.05,P<0.01),蜕膜组织细胞排列有序,水肿变性减轻,蜕膜组织VEGF、YAP、LATS1、LATS2 mRNA表达明显升高(P<0.05,P<0.01),VEGF蛋白表达明显升高(P<0.05,P<0.01),p-YAP/YAP、p-LATS/LATS蛋白表达明显降低(P<0.05,P<0.01)。结论补肾安胎合剂可能通过激活VEGF/Hippo/YAP信号通路促进VEGF、YAP、LATS等分子表达,促进母胎界面血管生成,降低妊娠丢失率,发挥治疗RSA作用。Objective To observe the effects of Bushen Antai Mixture on angiogenesis at the maternal fetal interface in recurrent spontaneous abortion(RSA)mice;To explore its mechanism in treating RSA based on the VEGF/Hippo/YAP pathway.Methods RSA mouse model and normal pregnancy mouse were constructed using Clark classic method.RSA model mice were randomly divided into model group,progesterone group,Bushen Antai Mixture low-,medium-and high-dosage groups,and normal pregnant mice were used as normal group,with 10 mice in each group.Starting from the first day of pregnancy,each medication group was given the corresponding medication by gavage for 15 days.The absorption rate of mouse embryos was calculated,the morphology of decidual tissue were observed by HE staining,the mRNA and protein expression of VEGF and Hippo/YAP pathway-related molecules of decidual tissue were detected by RT-qPCR and Western blot.Results Compared with the normal group,the absorption rate of embryos in the model group significantly increased(P<0.01),the arrangement of decidual tissue cells were disordered,edematous and degenerated,some nuclei disappeared,the vascular density decreased,the mRNA expressions of VEGF,Yes associated protein(YAP),large tumor suppressor factor(LATS)1 and LATS2 in decidual tissue significantly decreased(P<0.01),the protein expression of VEGF decreased(P<0.01),and the protein expressions of p-YAP/YAP and p-LATS/LATS significantly increased(P<0.01).Compared with the model group,the absorption rate of embryos in each dosage group of Bushen Antai Mixture was significantly reduced(P<0.05,P<0.01),the cells in the decidual tissue were arranged in an orderly manner,and edema degeneration was reduced,the mRNA expressions of VEGF,YAP,LATS1 and LATS2 in decidual tissue significantly increased(P<0.05,P<0.01),and the protein expression of VEGF significantly increased(P<0.05,P<0.01),the protein expressions of p-YAP/YAP and p-LATS/LATS decreased(P<0.05,P<0.01).Conclusion Bushen Antai Mixture can promote the expressions of VEGF,YAP,LATS by

关 键 词：补肾安胎合剂 复发性流产 Hippo/YAP通路 血管内皮生长因子 血管新生 小鼠 

分 类 号：R285.5[医药卫生—中药学]