黄芪对孕鼠缺氧型子痫前期的治疗作用观察及其主要活性成分和核心靶基因筛选  

Therapeutical effect of astragalus on hypoxic preeclampsia in pregnant mice and screening of its active ingredients and core target

作　　者：汪涛[1] 李博 吕菁菁[1] 申永梅 聂茂林 赵振营[5] WANG Tao;LI Bo;LU Jingjing;SHEN Yongmei;NIE Maolin;ZHAO Zhenying(Department of Pharmacy,Tianjin Central Hospital of Obstetrics and Gynecology,Tianjin 300100,China;不详)

机构地区：[1]天津市中心妇产科医院药剂科,天津300100 [2]天津中医药大学中医系 [3]天津市人类发育与生殖调控重点实验室妇产科研究所/天津市中心妇产科医院 [4]天津医科大学临床医学院 [5]天津市人民医院药学部

出　　处：《山东医药》2024年第36期11-16,23,共7页Shandong Medical Journal

基　　金：天津市卫生和计划生育委员会中医中西医结合科研课题(2021169)。

摘　　要：目的通过孕鼠缺氧型子痫前期(PE)实验研究黄芪对PE的治疗作用,结合网络药理学方法探索潜在靶点和作用机制,为PE的预防和治疗提供新思路。方法构建孕鼠PE模型,设空白对照组、模型组(0.01 mL/g蒸馏水)及阳性对照组[0.013 mg/(g·d)阿司匹林]、黄芪低剂量组(3.9 mg/g黄芪)和黄芪高剂量组(15.6 mg/g黄芪),妊娠第7天开始给药并测量血压,妊娠17天处死,取出胎鼠和胎盘,记录胎鼠出生体质量、计算宫内生长受限率(IUGR);HE染色观察胚胎滋养细胞形态和血管形态;荧光定量PCR方法检测胎盘组织低氧诱导因子(HIF-1α)、可溶性血管内皮生长因子受体-1(sFLT-1)以及胎盘生长因子(PLGF)的mRNA表达量。利用TCMSP平台和Gene cards等数据库获得黄芪主要活性成分和PE疾病交集靶点基因,构建“黄芪药物成分—PE疾病靶点”网络和蛋白质—蛋白质相互作用关系(PPI)网络,获取核心靶点基因;进行GO和KEGG代谢通路富集分析。结果与空白对照组比较,其余4组胎鼠体质量降低(P均<0.05);与模型组比较,黄芪高剂量组和空白对照组孕鼠血压降低,其余4组胎鼠体质量升高(P均<0.05);与阳性对照组比较,黄芪高剂量组和模型组胎鼠体质量降低,黄芪低剂量组和空白对照组胎鼠体质量升高(P均<0.05);与黄芪低剂量组比较,黄芪高剂量组和模型组胎鼠体质量降低,空白对照组胎鼠体质量升高(P均<0.05);与黄芪高剂量组比较,模型组胎鼠体质量降低,黄芪低剂量组、阳性对照组、空白对照组胎鼠体质量升高(P均<0.05)。与模型组比较,黄芪低剂量组、阳性对照组IUGR率降低(P均<0.05)。空白对照组血管分布密集,存在大量滋养细胞;模型组孕鼠胎盘组织中滋养细胞及血管显著减少、有微血栓形成、局部梗死、胎盘绒毛间隙广泛纤维素渗出;阳性对照组和黄芪低剂量组孕鼠胎盘组织中血管分布密集,血运丰富;黄芪高剂量组孕鼠局部纤维�Objective To investigate the therapeutic effect of astragalus on hypoxic preeclampsia(PE)in pregnant mice,to explore potential targets and mechanisms combined with network pharmacology methods,and to provide new ideas for the prevention and treatment of PE.Methods PE models of pregnant mice were established,and they were dicided into the blank control group,model group(0.01 mL/g distilled water),positive control group[0.013 mg/(g·d)aspirin],low-dose astragalus group(3.9 mg/g astragalus),and high-dose astragalus group(15.6 mg/g astragalus).The mice were given medication and their blood pressures were measured on the 7th day of gestation.The mice were euthanized on the 17th day of gestation.The fetal mice and placentas were collected,the birth mass of fetal mice was recorded,and the intrauterine growth restriction(IUGR)rate was calculated.We observed the morphology of embryonic trophoblast cells and blood vessels by HE staining.The mRNA expression levels of hypoxia-inducible factor-1α(HIF-1α),soluble vascular endothelial growth factor receptor-1(sFLT-1)and placental growth factor(PLGF)in placental tissues were detected by fluorescent quantitative PCR method.TCMSP platform and Gene cards database were used to obtain the intersection target genes of main active ingredients of astragalus and PE disease,and the"Astragalus ingredient-PE disease target"network and protein-protein interaction(PPI)network were constructed to obtain the core target genes,and enrichment analysis of GO and KEGG metabolic pathways were performed.Results Compared with the blank control group,the body mass of the other four groups decreased(P<0.05).Compared with the model group,the blood pressure of pregnant mice in the high-dose Astragalus group and blank control group decreased,and the body mass of fetal mice in the other four groups increased(all P<0.05).Compared with the positive control group,the fetal body mass of the high-dose astragalus group and model group decreased,while the fetal body mass of the low-dose astragalus group and blan

关 键 词：黄芪 子痫前期 网络药理学 缺氧 

分 类 号：R969[医药卫生—药理学]