阿司匹林对早发子痫前期外泌体诱导滋养细胞功能的作用  

The effect of aspirin on exosome-induced trophoblast function in early-onset preeclampsia

作　　者：黄亭 周伟 朱锦明[3] 石祥奎 HUANG Ting;ZHOU Wei;ZHU Jinming;SHI Xiangkui(Pharmaceutical Affairs Department,Xuzhou Maternity and Child Health Care Hospital,Xuzhou,Jiangsu 221009,China;Center of Genetic medicine,Xuzhou Maternity and Child Health Care Hospital,Xuzhou,Jiangsu 221009,China;Obstetrics Department,Xuzhou Maternity and Child Health Care Hospital,Xuzhou,Jiangsu 221009,China)

机构地区：[1]徐州市妇幼保健院药事科,江苏徐州221009 [2]徐州市妇幼保健院医学遗传与产前诊断科,江苏徐州221009 [3]徐州市妇幼保健院产科,江苏徐州221009

出　　处：《中国优生与遗传杂志》2023年第4期696-701,共6页Chinese Journal of Birth Health & Heredity

基　　金：徐州市科技计划项目(KC20065);徐州医科大学附属医院科技发展基金项目(XYFY2021022)。

摘　　要：目的 构建子痫外泌体细胞模型研究阿司匹林改善滋养细胞功能并预防子痫前期(PE)的作用及分子机制。方法 收集早发型PE病例14例和正常孕妇作为对照8例,提取血浆外泌体。体外培养人滋养细胞HTR-8/SVneo,分别加入不同浓度的PE外泌体造模并给予阿司匹林处理;CCK-8法检测滋养细胞增殖情况;细胞划痕和Transwell小室检测滋养细胞迁移、侵袭变化;RT-qPCR和Western blot检测血管内皮生长因子(VEGF)mRNA和蛋白表达水平情况;ELISA法检测孕妇血浆VEGF水平。结果 PE外泌体可以显著抑制滋养细胞活力,且PE孕妇血浆中VEGF浓度低于NC组。体外PE外泌体滋养细胞模型实验证实,与NC组相比,100μg/mL PE外泌体显著抑制滋养细胞增殖、影响滋养细胞迁移、侵袭能力,抑制内皮细胞HUVEC小管形成功能,降低VEGF的表达(P<0.001);而给予阿司匹林处理后,滋养细胞增殖、迁移、侵袭能力以及内皮细胞小管形成功能均改善。结论 阿司匹林提高滋养细胞增殖、迁移和侵袭能力,改善PE外泌体诱导后滋养细胞功能损伤,提高VEGF水平。这为阿司匹林用于早发型PE的预防、治疗提供了实验依据。Objective To investigate the effect and molecular mechanism of aspirin in improving the function of trophoblast cells and preventing preeclampsia(PE)through cell model treated with PE exosomes in vitro.Methods Plasma exosomes were extracted from 8 cases of early-onset PE and 14 of normal pregnant women.Human trophoblast cells HTR-8/SVneo were cultured in vitro,and PE exosomes at different concentrations were added and treated with aspirin.CCK-8 assay was utilized to detect the proliferation of trophoblast cells.Cell scratch and Transwell chamber were chosen to detect the migration and invasion of trophoblast cells.RT-qPCR and Western blot were used to detect the mRNA and protein expression of vascular endothelial growth factor(VEGF).Serum VEGF levels were identified by ELISA.Results PE exosomes could significantly inhibit the viability of trophoblast cells,and the plasma concentration of VEGF in PE pregnant women was lower than that in the NC group.In vitro experiments of PE exosome trophoblast cell model confirmed that compared with the NC group,100μg/mL PE exosome significantly inhibited the proliferation of trophoblast cells,affected the migration and invasion ability of trophoblast cells,inhibited the tubule formation function of endothelial cells HUVEC,and decreased the expression of VEGF(P<0.001).After treated with aspirin,the proliferation,migration,invasion and tubule formation of trophoblast cells were improved.Conclusion Aspirin can promote the ability of trophoblast proliferation,migration and invasion,improve the functional injury of trophoblast after PE exosome induction,and increase the level of VEGF.This provides experimental evidence for aspirin in the prevention and treatment of early-onset PE.

关 键 词：阿司匹林 早发子痫 外泌体 滋养细胞 

分 类 号：R714.244[医药卫生—妇产科学]