减味寿胎丸介导PI3K/AKT/mTOR信号通路对米非司酮诱导HTR-8/SVneo细胞损伤模型血管生成功能的影响  

Effects of Jianwei Shoutai Pills-mediated PI3K/AKT/mTOR signaling pathway on angiogenic function in Mifepristone induced HTR-8/SVneo cell injury model

作　　者：黄娴 曾丽华 谢宝珍 李经纬 郜洁[2] 罗颂平[2] HUANG Xian;ZENG Lihua;XIE Baozhen;LI Jingweil;GAO Jie;LUO Songping(First School of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The First Affliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]广州中医药大学第一临床医学院,广州510405 [2]广州中医药大学第一附属医院,广州510405

出　　处：《中华中医药杂志》2024年第9期4664-4669,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.82174424);青年岐黄学者培养项目(No.国中医药人教函[2022]256号);广东省重点领域研发计划“岭南中医药现代化”重点专项(No.2020B1111100003);广州市基础研究计划市校(院)联合资助市重点实验室建设项目(No.202201020383)。

摘　　要：目的:探讨减味寿胎丸通过调控PI3K/AKT/mTOR信号通路对米非司酮诱导HTR-8/SVneo细胞损伤模型血管生成功能的影响。方法:收集自然流产患者以及正常妊娠女性绒毛组织各20例。构建米非司酮诱导HTR-8/SVneo细胞损伤模型,分为阴性对照组、模型组、孕酮组和减味寿胎丸组。采用CCK8法检测米非司酮对HTR-8/SVneo细胞以及减味寿胎丸对米非司酮诱导HTR-8/SVneo细胞损伤模型细胞增殖活力的影响。Western Blot测定血管内皮生长因子A(VEGFA)、血管内皮生长因子受体(VEGFR)1、VEGFR2以及信号通路PI3K、p-AKT、p-mTOR蛋白的表达。结果:与正常妊娠女性比较,自然流产患者绒毛组织VEGFA、VEGFR1、VEGFR2以及PI3K、p-AKT、p-mTOR信号通路蛋白的表达显著下调(P<0.05,P<0.01);不同浓度减味寿胎丸作用24 h均能显著增加米非司酮诱导HTR-8/SVneo细胞损伤模型的细胞活性(P<0.05,P<0.01);米非司酮诱导HTR-8/SVneo细胞损伤模型血管生成功能相关蛋白VEGFA、VEGFR1与VEGFR2蛋白表达显著下调(P<0.01,P<0.05),PI3K信号通路蛋白表达显著下降(P<0.01),而减味寿胎丸能提高上述模型血管生成功能相关蛋白与PI3K/AKT/mTOR信号通路蛋白表达(P<0.01,P<0.05)。结论:减味寿胎丸可能通过介导PI3K/AKT/mTOR信号通路提高米非司酮诱导HTR-8/SVneo细胞损伤模型VEGFA及其受体表达,从而起到补肾安胎作用。Objective:To investigate the effects of Jianwei Shoutai Pills in regulating PI3K/AKT/mTOR signaling pathway on the angiogenic function of Mifepristone induced HTR-8/SVneo cell injury model.Methods:Twenty chorionic villus tissues were collected from spontaneous abortion patients(SA)and normal pregnant females(NP)respectively.A Mifepristoneinduced HTR8-SVneo cell injury model was constructed and divided into negative control group,model group,progesterone group,and Jianwei Shoutai Pills group.The effects of Mifepristone on the growth of HTR-8/SVneo cells and the effects of Jianwei Shoutai Pills on the growth of Mifepristone-induced HTR-8/SVneo cell injury models were detected by CCK8.The expression of vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor receptor(VEGFR)1,VEGFR2,and the signaling pathway PI3K,p-AKT,and p-mTOR-related proteins were measured by Western Blot.Results:The expression of VEGFA,VEGFR1,VEGFR2 and signaling pathway PI3K,p-AKT,p-mTOR related proteins were down-regulated in the chorionic villus tissues of spontaneous abortion patients compared to normal pregnant women(P<0.05,P<0.01);Different concentrations of Jianwei Shoutai Pills for 24 hours increased the activity of mifepristone induced HTR-8/SVneo cell injury model(P<0.05,P<0.01);VEGFA,VEGFR1 and VEGFR2 expression were downregulated in the Mifepristone induced HTR-8/SVneo cell injury model(P<0.05,P<0.01),and PI3K signaling pathway protein expression was decreased(P<0.01),while Jianwei Shoutai Pills increased the model angiogenic function related protein and PI3K/AKT/mTOR signaling pathway protein expression(P<0.01,P<0.05).Conclusion:The Jianwei Shoutai Pills may increase the expression of VEGFA and its receptor in the Mifepristone-induced HTR-8/SVneo cell injury model through mediating the PI3K/AKT/mTOR signaling pathway,thus playing a role in tonifying the kidney and calming the fetus.

关 键 词：减味寿胎丸 米非司酮 滋养细胞 血管生成 自然流产 

分 类 号：R285.6[医药卫生—中药学]