天麻素调控Notch通路对妊娠期高血压大鼠胎盘血管生成及妊娠结局的影响  

Impacts of gastrodin on placental angiogenesis and pregnancy outcomes in pregnancy induced hypertension rats by regulating the Notch pathway

作　　者：杨旋[1] 张文娟[2] 夏丽 YANG Xuan;ZHANG Wenjuan;XIA Li(Center of Information,Women's Hospital School of Medicine Zhejiang University,Hangzhou,310006,China;Center of Information,Shaw Hospital Affiliated to Zhejiang University School of Medicine,Hangzhou 310016,China;Department of Obstetrics and Gynecology,Hangzhou First People's Hospital Affiliated to Zhejiang University School of Medicine,Hangzhou 310003,China)

机构地区：[1]浙江大学医学院附属妇产科医院信息中心 [2]浙江大学医学院附属邵逸夫医院信息中心 [3]浙江大学医学院附属杭州市第一人民医院妇产科

出　　处：《中国妇产科临床杂志》2025年第2期139-143,共5页Chinese Journal of Clinical Obstetrics and Gynecology

摘　　要：目的探讨天麻素(gastrodin,Gas)调控Notch通路对妊娠期高血压(PIH)大鼠胎盘血管生成及妊娠结局的影响。方法受孕大鼠皮下注射L-精氨酸甲酯(L-NAME)构建PIH模型,造模成功后,按照随机数字表法分成模型组、Gas低、中、高剂量组(50、100、200 mg/kg)、抑制剂组(Gas 200 mg/kg+Notch通路抑制剂γ-分泌酶抑制剂500μg/100 g),选取同期孕鼠作为对照组,各组腹腔注射相应药物,每天1次连续1周。血压测量仪、邻苯三酚红法分别检测妊娠晚期尾静脉压、24 h尿蛋白;妊娠第24天进行剖宫产;采用CD34染色检测胎盘组织微血管数量及密度;酶联免疫吸附测定胎盘组织白细胞介素(IL)-6、IL-1β和肿瘤坏死因子(TNF-α)水平;蛋白印迹法测定胎盘组织血管内皮生长因子(VEGF)及Notch通路蛋白表达。结果与模型组相比,Gas低、中、高剂量组24 h尿蛋白、尾静脉压、IL-1β、IL-6和TNF-α水平下降,平均胎鼠质量、平均子代数、微血管数量(MVQ)、微血管密度(MVD)、VEGF、Notch1、Jagged1和hes家族bHLH转录因子1(HES1)表达升高(P<0.05),各组间比较,差异均有统计学意义(P<0.05);与Gas高剂量组相比,抑制剂组大鼠上述指标变化均逆转(P<0.05)。结论Gas具有抑制炎症、促进PIH大鼠血管生成,改善妊娠结局的作用,其作用机制可能与激活Notch通路有关。Objective To investigate the impacts of gastrodin(Gas)on placental angiogenesis and pregnancy outcomes in pregnancy induced hypertension(PIH)rats by regulating the Notch pathway.Methods A PIH model was constructed by subcutaneous injection of L-arginine methyl ester(L-NAME)into pregnant rats,after successful modeling,the model was grouped into model group,Gas low,medium,and high dose groups(50,100,200 mg/kg),and inhibitor group(Gas 200 mg/kg+Notch pathway inhibitor gamma-secretase inhibitor 500)using a random number table methodμg/100 g),12 mice/group,12 pregnant mice of the same period were regarded as the control group,and each group was injected with corresponding drugs intraperitoneally,once a day for one consecutive week.Blood pressure measuring instruments and pyrogallol red method were applied to detect tail vein pressure and 24-hour urine protein in late pregnancy,respectively;cesarean section was performed on the 24 th day of pregnancy,and the pregnancy outcome was recorded;Hematoxylin eosin staining was applied to observe pathological changes in placental tissue;CD34 staining was applied to detect the number and density of microvessels in placental tissue;enzyme-linked immunosorbent assay was applied to detect levels of interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α)in placental tissue;Western blot was applied to detect the expression of vascular endothelial growth factor(VEGF)and Notch pathway proteins in placental tissue.Results Compared with the model group,24-hour urine protein,the tail vein pressure,IL-1β,IL-6,and TNF-αlevels in the low,medium,and high dose Gas groups were reduced,the average fetal rats mass,average offspring number,microvessel quantity(MVQ),microvessel density(MVD),VEGF,Notch1,Jagged1,hes family bHLH transcription factor 1(HES1)expression were increased,there was a statistical difference between each group(P<0.05);compared with the high-dose gas group,the changes in the above indicators in the inhibitor group were reversed(P<0.05).Conclusions Gas has the effects o

关 键 词：天麻素 NOTCH通路 妊娠期高血压 血管生成 妊娠结局 

分 类 号：R71[医药卫生—妇产科学]