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减味寿胎丸对流产模型大鼠母胎界面血管生成功能的影响OA

Effects of Jianwei Shoutai Pill(减味寿胎丸)on vascular angiogenic function at the maternal-fetal interface in abortion model rats

中文摘要英文摘要

目的 探讨减味寿胎丸对流产模型大鼠母胎界面血管生成功能的影响.方法 构建米非司酮诱导的大鼠流产模型,对其进行地屈孕酮、减味寿胎丸干预.将实验动物分为对照组(Control),流产模型组(Model),地屈孕酮阳性对照组(Positive),减味寿胎丸干预组(JW).除Control组外,其余各组孕鼠在妊娠第13天给予1.2mg·mL-1的米非司酮药液灌胃(10ml·kg-1)构建流产大鼠模型.自妊娠第0天至第14天,给予Control组和Model组灌胃0.5%的CMC-Na 溶液;给予Positive组灌胃0.54mg·mL-1的地屈孕酮药液,给予JW组灌胃180 mg·mL-1减味寿胎丸药液.体视镜观察各组孕鼠子宫及胚胎形态,计算各组孕鼠胚胎丢失率,采用小动物超声测量孕鼠脐血流每博输出量,免疫组化及Western blot检测各组孕鼠蜕膜组织中血管生成因子及Notch-1/Dll4、PI3K/AKT通路蛋白的表达.结果 Control组子宫颜色呈淡红色,形态粗大似串珠,宫腔及胚胎着床点未见明显瘀血点,胚胎形态饱满红润,表面可观察到清晰的血管及其分支,血供丰富;与Control 相比,Model组子宫颜色发黯,子宫部分节段未见胚胎存在,形态似竹节,剖开可见有管腔及胚胎着床位点散在分布的瘀血点,胚胎本身可见瘀血点,胚胎出现皱缩,颜色发白,血管及其分支明显减少;与Model 组相比,Positive、JW 组子宫颜色明显红润,形态较规则,剖开可见有管腔及胚胎着床位点散在少量的瘀血点,胚胎形态较饱满,颜色转红,可见明显的血管及其分支.与Control组相比,Model组胚胎丢失率明显升高,脐血流每博输出量显著下降,免疫组化及Western blot中VEGFA、VEGFR1与VEGFR2蛋白表达显著下调(P<0.05),Western blot中Notch-1、PI3K、AKT表达均有所降低(P<0.05),Dll4表达无明显差异;与Model组相比,Positive和JW组胚胎丢失率均显著下降,脐血流每博输出量显著提升,免疫组化及Western blot中VEGFA、VEGFR1与VEGFR2蛋白表达明显升高(P<0.05);与Model组相比,Positive组Notch-1及Dll4表达均无明显差异,PI3K及AKT表达均有明显上升;与Model组相比,JW组Notch-1及PI3K、AKT表达均有明显上升,Dll4表达无明显差异.结论 减味寿胎丸可明显降低米非司酮诱导的大鼠流产模型的胚胎丢失率,推测可能是减味寿胎丸通过Notch及PI3K/AKT通路影响血管生成功能来防治自然流产的发生.

Objective To explore the effect of Jianwei Shoutai Pill(减味寿胎丸,JWSTP/JW)on the angiogenic function at the maternal-fetal interface in the rats model of abortion.Methods The rats model of abortion were established by induction of mifepristone.The rats were then treated with dydrogesterone or JWSTP.The rats were divided into the control group(Control),the abortion model group(Model),the positive control group treated with dydrogesterone(Positive),and the group treated with JWSTP.Except for the Control group,the other groups were given 1.2 mg/mL mifepristone solution by gavage on the 13th day of pregnancy to establish the abor-tion model.From the 0th to the 14th day of pregnancy,the Control and Model groups were given 0.5%CMC-Na solution by gavage,the Positive group was given 0.54 mg/mL dydrogesterone solution by gavage,and the JW group was given 180 mg/mL JWSTP solution by gavage.The uterine and embryo morphology of each group was observed under a stereomicroscope,and the embryo loss rate was calcu-lated.The stroke volume of umbilical blood flow in pregnant rats was measured by small animal ultrasound.The expression of angio-genic factors and Notch-1/Dll4,PI3K/AKT pathway proteins in the decidua tissue of pregnant rats in each group was detected by immu-nohistochemistry(IHC)and Western blot(WB).Results The uterus of the Control group was light red in color,with a thick and bead-like shape.No pronounced blood stasis points were observed in the uterine cavity and embryo implantation sites,and the embryos were plump and rosy with clear blood vessels and branches,and rich blood supply.Compared with the Control group,the uterus of the Model group was dark in color,with some segments of the uterus showing no embryos,and a bamboo-like shape.When dissected,scattered blood stasis points were observed in the uterine cavity and embryo implantation sites,and the embryos themselves had blood stasis points,were shriveled,and pale in color,with significantly reduced blood vessels and branches.Compared with the Model group,the uterus of the Positive and JWSTP groups was significantly more rosy in color and regular in shape.When dissected,only a few scattered blood stasis points were observed in the uterine cavity and embryo implantation sites,and the embryos were plump,with a reddish color,and obvious blood vessels and branches.Compared with the Control group,the embryo loss rate in the Model group was signifi-cantly increased,the stroke volume of umbilical blood flow decreased significantly,and the expression of VEGFA,VEGFR1,and VEGFR2 proteins was significantly downregulated in IHC and WB(P<0.05),in WB,the expressions of Notch-1,PI3K and AKT were all decreased(P<0.05),while there was no significant difference in the expression of Dll4;Compared with the Model group,the embryo loss rate in the Positive and JWSTP groups was significantly decreased,the stroke volume of umbilical blood flow has signifi-cantly increased,and the expression of VEGFA,VEGFR1,and VEGFR2 proteins was significantly increased in IHC and WB(P<0.05);Compared with the Model group,there were no significant differences in the expression of Notch-1 and Dll4 in the Positive group,while the expressions of PI3K and AKT significantly increased;compared with the Model group,the expressions of Notch-1 and PI3K,AKT in the JWSTP group significantly increased,while the expression of Dll4 showed no significant difference.Conclusion JWSTP can significantly reduce the embryo loss rate in the mifepristone-induced rats abortion model.It is speculated that the reduction of teratogenic effects in JWSTP may occur through the Notch and PI3K/AKT pathways,thereby influencing the vascular growth function and preventing the occurrence of spontaneous abortion.

吕孝丽;周月希;谢宝珍;郜洁;罗颂平

河南省中医院,河南 郑州 450002||广州中医药大学第一临床医学院,广东 广州 510405广州中医药大学第一临床医学院,广东 广州 510405||武汉市第一医院,湖北 武汉 430030广州中医药大学第一临床医学院,广东 广州 510405广州中医药大学第一附属医院,广东 广州 510405广州中医药大学第一附属医院,广东 广州 510405

医药卫生

减味寿胎丸自然流产母胎界面血管生成

Jianwei Shoutai Pill(减味寿胎丸)Spontaneous abortionMaternal-fetal InterfaceAngiogenesis

《时珍国医国药》 2026 (13)

2416-2423,8

国家自然科学基金面上项目(82174424,82374502,81873336)河南省中医院博士科研基金(2022BSJJ05)

10.70976/j.1008-0805.SZGYGY-2026-1303

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