葫芦巴碱的预防性使用可减轻妊高症大鼠模型的症状并保护胎儿生长和血管内皮功能  

The preventive use of trigonelline can alleviate symptoms in a rat model of pregnancy-induced hypertension and protect fetal growth

作　　者：史许锋 刘侃[1] 王莉[1] 王焕萍[1] 张敬丽 武海英[1] SHI Xufeng;LIU Kan;WANG Li;WANG Huanping;ZHANG Jingli;WU Haiying(Department of Obstetrics,Henan Provincial People’s Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院产科,郑州450003

出　　处：《中国比较医学杂志》2021年第7期62-70,共9页Chinese Journal of Comparative Medicine

基　　金：河南省医学科技攻关计划联合共建项目(2018020417)。

摘　　要：目的旨在确定妊娠早期使用葫芦巴碱对于一氧化氮合酶拮抗剂N-硝基-1-精氨酸甲酯(LNAME)诱导的PE大鼠的治疗作用。方法在妊娠第0天,将28只Sprague-Dawley(SD)大鼠随机分为4组,怀孕对照组,LNAME诱导的PE组和预防性使用葫芦巴碱的小剂量组和大剂量组;测量孕鼠血压和蛋白尿并通过股动脉超声评估孕鼠内皮功能,通过ELISA检测炎症因子和内皮相关因子的表达,最后收获孕鼠胎盘和肾进行免疫组化分析,同时通过实时荧光定量PCR(RT-qPCR)和蛋白免疫印迹法(Western blot)分析炎症相关通路状态。结果预防性给予小剂量和高剂量葫芦巴碱可改善LNAME引起的高血压、蛋白尿、孕期大鼠体重减轻、胎儿生长受限和血流介导的扩张,而葫芦巴碱可能通过途径IκBα/NF-κB而平衡内皮相关因子并减轻胎盘和肾组织中的炎症活化。结论葫芦巴碱在LNAME诱导的PE样大鼠模型中的预防性使用可减轻PE症状,促进胎儿生长,保护内皮功能并减少炎症。Objective To determine the therapeutic effect of trigonelline in early pregnancy on rats with preeclampsia(PE)induced by the nitric oxide synthase antagonist N-nitro-1-arginine methyl ester(LNAME).Methods On day zero of pregnancy,28 Sprague-Dawley rats were randomly assigned to four groups:pregnancy control group,LNAME-induced PE group,and prophylactic use of trigonelline small dose group and high-dose group.Blood pressure and proteinuria of the pregnant rats were measured,endothelial function of pregnant rats was evaluated by femoral artery ultrasound,and the expression of inflammatory factors and endothelial-related factors were detected by ELISA.Finally,the placenta and kidney of pregnant rats were harvested for immunohistochemical analysis and to analyze the status of inflammation-related pathways by Real-time fluorescent quantitative PCR and Western blot.Results Prophylactic administration of low-dose or high-dose trigonelline improved hypertension,proteinuria,and weight loss during pregnancy,fetal growth restriction and blood flow-mediated dilation caused by LNAME.Trigonelline may act through the IκBα/NF-κB pathway,balance endothelium-related factors and reduce inflammation activation in placenta and kidney tissues.Conclusions The preventive use of trigonelline in a PE-like rat model induced by LNAME can reduce PE symptoms,promote fetal growth,protect endothelial function and reduce inflammation.

关 键 词：葫芦巴碱 先兆子痫 内皮功能 蛋白尿 妊娠早期 

分 类 号：R-33[医药卫生]