Notch信号通路激活状态与Th17/Treg失衡在胎儿宫内生长受限发病机制中的作用研究OA
Role of Notch signaling pathway activation and Th17/Treg imbalance in the pathogenesis of fetal intrauterine growth restriction
目的 探讨Notch同源物1(Notch 1)信号通路激活状态与辅助性T细胞(Th)17/调节性T细胞(Treg)失衡在胎儿宫内生长受限(IUGR)发病机制中的作用.方法 前瞻性选取2023年1月至2024年10月在金华市中心医院接受治疗的IUGR孕妇30例(IUGR组),并选取同期本院妊娠第三期正常孕妇30名(正常妊娠组)和健康未孕女性30名(健康未孕组),采集血液样本.采用流式细胞术检测3组研究对象外周血中Th17与Treg比例及CD4+Notch1+毛状和分裂增强子-1(Hes-1)+细胞比例,采用酶联免疫吸附试验(ELISA)检测血清白细胞介素-17(IL-17)、转化生长因子-β(TGF-β)水平,采用蛋白质印迹(Western blot)法检测外周血中Notch 1和Hes1蛋白表达水平.动物实验部分将大鼠分为对照组、IUGR组及IUGR+Notch抑制剂组(IUGR+抑制剂组),检测3组大鼠胎鼠及胎盘重量,采用流式细胞术检测大鼠外周血中Th17与Treg细胞比例及CD4+Notch1+Hes1+细胞比例,采用ELISA检测血清IL-17与TGF-β水平,采用Western blot法检测外周血中Notch 1与Hes1蛋白表达水平.结果 与正常妊娠组和健康未孕组相比,IUGR组患者Th17比例升高,Treg比例降低,Th17/Treg比例升高,血清中IL-17水平升高,TGF-β水平降低,Notch 1和Hes1蛋白表达水平均升高,差异均有统计学意义(均P＜0.01).动物实验中,与对照组相比,IUGR组大鼠胎鼠和胎盘重量均减少,Th17比例升高,Treg比例降低,Th17/Treg比例升高,血清中IL-17水平升高,TGF-β水平降低,Notch 1和Hes1蛋白表达水平均升高,差异均有统计学意义(均P＜0.01).经Notch信号通路抑制剂干预后,与IUGR组相比,IUGR+抑制剂组大鼠胎鼠和胎盘重量均增加,Th17比例降低,Treg比例升高,Th17/Treg比例降低,血清中IL-17水平降低,TGF-β水平升高,Notch 1和Hes1蛋白表达水平均降低,差异均有统计学意义(均P＜0.01).结论 Notch信号通路激活与Th17/Treg失衡在IUGR发病机制中有重要作用,可为早期诊断和治疗提供潜在靶点.
Objective To investigate the role of notch homolog 1(Notch1)signaling pathway activation and T helper cell 17(Th17)/regulatory T cell(Treg)imbalance in the pathogenesis of fetal intrauterine growth restriction(IUGR).Methods A prospective study was conducted,enrolling 30 pregnant women with IUGR(IUGR group)treated at Jinhua Municipal Central Hospital from January 2023 to October 2024,along with 30 normal pregnant women in the third trimester(normal pregnancy group)and 30 healthy non-pregnant women(healthy non-pregnant group)during the same period.Blood samples were collected from all participants.Flow cytometry was used to detect the proportions of Th17 and Treg and CD4+Notch1+hairy and enhancer of split-1(Hes-1)+cells in peripheral blood.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum interleukin-17(IL-17)and transforming growth factor-β(TGF-β)levels.Western blot was used to detect Notch1 and Hes1 protein expression levels in peripheral blood.In the animal experiment,rats were divided into a control group,an IUGR group,and an IUGR+Notch inhibitor group(IUGR+inhitor group).Fetal and placental weights were measured,and flow cytometry,ELISA,and Western blot were used to assess the same indicators as in the human study.Results Compared with the normal pregnancy and healthy non-pregnant groups,the IUGR group showed significantly increased Th17 proportion,decreased Treg proportion,elevated Th17/Treg ratio,increased serum IL-17 levels,decreased TGF-β levels,and upregulated Notch1 and Hes1 protein expression levels(all P＜0.01).In the animal experiment,compared with the control group,the IUGR group exhibited reduced fetal and placental weights,increased Th 17 proportion,decreased Treg proportion,elevated Th17/Treg ratio,increased serum IL-17 levels,decreased TGF-β levels,and upregulated Notch1 and Hes1 protein expression levels(all P＜0.01).After Notch signaling pathway inhibitor intervention,compared with the IUGR group,the IUGR+inhibitor group showed increased fetal and placental weights,decreased Th17 proportion,increased Treg proportion,reduced Th17/Treg ratio,decreased serum IL-17 levels,increased TGF-β levels,and downregulated Notch1 and Hes1 protein expression levels(all P＜0.01).Conclusion Notch signaling pathway activation and Th 17/Treg imbalance play important roles in the pathogenesis of IUGR,providing potential targets for early diagnosis and treatment.
晏婷;袁里朝;施展华;吕英
321000 金华市中心医院产科321000 金华市中心医院产科321000 金华市中心医院产科321000 金华市中心医院产科
胎儿宫内生长受限Notch信号通路辅助性T细胞17/调节性T细胞失衡
Fetal intrauterine growth restrictionNotch signaling pathwayT helper cell 17/regulatory T cell imbalance
《浙江医学》 2026 (2)
117-125,9
金华市科技计划项目(2021-3-124)
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