补肾活血方调控复发性流产小鼠母胎界面血管生成实验研究  

Experimental Study on Bushen Huoxue Prescription in the Regulation of MaternalFetal Interface Angiogenesis in Mice with Recurrent Spontaneous Abortion

作　　者：李久现[1] 陈萍[1] 徐广立 孙建华[1] 刘玉楠[1] LI Jiuxian;CHEN Ping;XU Guangli;SUN Jianhua;LIU Yunan

机构地区：[1]河南中医药大学第一附属医院,河南郑州450000

出　　处：《新中医》2022年第17期1-7,共7页New Chinese Medicine

基　　金：国家自然科学基金项目(82074167);河南省高等学校重点科研项目(20A360003);河南省中医管理局国家中医临床研究基地科研专项(2018JDZX070);国家中医药管理局全国中医药创新骨干人才培训项目(国中医药人教函[2019]128号)。

摘　　要：目的:观察补肾活血方对复发性流产(RSA)小鼠血管内皮生长因子(VEGF)、可溶性血管内皮生长因子受体-1(sFlt-1)、缺氧诱导因子-1α(HIF-1α)、转化生长因子-β(TGF-β)的影响,探讨其降低流产率的作用机制。方法:构建RSA小鼠模型,将40只RSA模型小鼠随机分为模型组、补肾活血方低、中、高剂量组(6.53、13.06、26.13 g/kg)4组,每组10只,另取10只正常妊娠小鼠作空白组。补肾活血方低、中、高剂量组给予对应剂量的补肾活血方颗粒剂水溶液灌胃,空白组、模型组给予等容量蒸馏水灌胃,连续给药14 d后,处死小鼠,收集样本。观察各组小鼠胚胎丢失情况及蜕膜组织病理形态学改变;采用ELISA法检测血清VEGF、sFlt-1、HIF-1α、TGF-β含量;采用RT-PCR法检测蜕膜组织VEGF、sFlt-1、HIF-1α、TGF-βmRNA表达。结果:与空白组比较,模型组小鼠胚胎丢失率、血清HIF-1α、sFlt-1及蜕膜组织HIF-1α、sFlt-1 mRNA水平升高(P<0.05),蜕膜组织VEGF、TGF-βmRNA及血清VEGF、TGF-β水平降低(P<0.05);模型组小鼠蜕膜组织表现为细胞形态异常,排列紊乱,炎性细胞分布明显。与模型组比较,补肾活血方中、高剂量组小鼠胚胎丢失率、血清HIF-1α、sFlt-1及蜕膜组织HIF-1α、sFlt-1 mRNA水平降低(P<0.05),蜕膜组织VEGF、TGF-βmRNA及血清VEGF、TGF-β含量升高(P<0.05),其中补肾活血方高剂量组改善效果更为明显(P<0.05);经补肾活血方药物干预后,各给药组小鼠蜕膜组织的病理改变得到明显改善。结论:补肾活血方通过调节VEGF、TGF-β、sFlt-1及HIF-1α的表达来促进母胎界面血管生成,降低RSA小鼠流产率,起到保胎作用。Objective:To observe the effect of Bushen Huoxue prescription on vascular endothelial growth factors(VEGF),soluble fms-like tyrosine kinase receptor-1(sFlt-1),hypoxia inducible factor-1α(HIF-1α)and transforming growth factor-β(TGF-β)in mice with recurrent spontaneous abortion(RSA),and to explore its mechanism of reducing abortion rate.Methods:A total of 40 RSA mice models were randomly divided into the model group,the Bushen Huoxue prescription groups of low-dose,mediumdose and high-dose(6.53,13.06,26.13 g/kg),with 10 mice in each group,and 10 normal pregnant mice were involved in the blank group.The Bushen Huoxue prescription groups of low-dose,medium-dose and high-dose were given corresponding doses of Bushen Huoxue prescription granules aqueous solution by gavage,and the blank group and the model group were given equal volume distilled water by gavage.After 14 days of continuous administration,the mice were sacrificed and samples were collected.The loss of embryos and histopathological changes of decidua were observed.The levels of VEGF,sFlt-1,HIF-1αand TGF-βin serum were detected by ELISA.The mRNA expressions of VEGF,sFlt-1,HIF-1αand TGF-βin decidua tissue were detected by RT-PCR.Results:Compared with those in the blank group,the embryo loss rate,the levels of HIF-1αand sFlt-1 in serum,and mRNA expressions of HIF-1αand sFlt-1 in decidua tissue of mice in the model group were increased(P<0.05),and the mRNA expressions of VEGF and TGF-βin decidua tissue and levels of VEGF and TGF-βin serum were decreased(P<0.05);the decidua tissue of mice in the model group showed abnormal cell morphology,disordered arrangement and obvious distribution of inflammatory cells.Compared with those in the model group,the embryo loss rate,levels of HIF-1αand sFlt-1 in serum and mRNA expressions of HIF-1αand sFlt-1 in decidua tissue of mice in the Bushen Huoxue prescription groups of medium-dose and high-dose were decreased(P<0.05),and the mRNA expressions of VEGF and TGF-βin decidua tissue and levels of VEGF and TGF-β

关 键 词：复发性流产 补肾活血方 血管生成 血管内皮生长因子 缺氧诱导因子-1Α 

分 类 号：R285.5[医药卫生—中药学]