【摘要】 目的 探讨PIK3R1通过调控PI3K/AKT信号通路影响胎盘滋养层细胞凋亡在子痫前期（PE）发病中的作用机制。方法 采用RT-qPCR和免疫组化检测PE患者与正常胎盘滋养层组织中PIK3R1及相关通路分子的表达水平。TUNEL法检测胎盘组织滋养层细胞凋亡水平，Western blot检测PIK3R1、p-PI3K、PI3K、p-AKT/AKT及凋亡蛋白（BAX、BCL-2）的表达。选用HTR-8/SVneo细胞为模型，通过质粒转染敲低或过表达PIK3R1，利用q RT-PCR和Western blot验证干预效果及对PI3K/AKT通路的影响。CCK-8和Ed U实验分析细胞活力与增殖，TUNEL及Western blot检测细胞凋亡水平。在PIK3R1敲低细胞中加入PI3K/AKT激活剂IGF-1，观察通路恢复对细胞增殖和凋亡的挽救效应。结果 PE患者胎盘滋养层组织中PIK3R1表达显著下降，伴随凋亡增加、Bax上调、Bcl-2及p-PI3K/PI3K、p-AKT/AKT下调（P<0.05）。敲低PIK3R1抑制HTR-8/SVneo细胞增殖、促进凋亡并抑制PI3K/AKT通路（P<0.05）；过表达PIK3R1则呈现相反效应（P<0.05）。IGF-1激活PI3K/AKT可逆转PIK3R1敲低导致的细胞增殖抑制和凋亡增加（P<0.05）。结论 PIK3R1通过激活PI3K/AKT信号通路抑制胎盘滋养层细胞凋亡并促进增殖，其表达下调可能参与PE的发病机制。更多还原

【Abstract】 Objective To investigate the role of PIK3R1 in the pathogenesis of preeclampsia(PE)by regulating the PI3K/AKT signaling pathway and its impact on placental trophoblast cell apoptosis.Methods The expression levels of PIK3R1 and related pathway molecules in placental trophoblast tissues from PE patients and healthy controls were detected using RT-qPCR and immunohistochemistry.TUNEL assay was used to measure apoptosis levels,while Western blot(WB)was performed to analyze the expression of PIK3R1,p-PI3K,PI3K,p-AKT/AKT,and apoptosis-related proteins(BAX,BCL-2).HTR-8/SVneo cells were used as a model,with PIK3R1 knockdown or overexpression achieved via plasmid transfection.RT-qPCR and WB were used to verify transfection efficiency and assess PI3K/AKT pathway activity.Cell viability and proliferation were evaluated using CCK-8 and EdU assays,while apoptosis was detected by TUNEL and WB.To further explore the regulatory role of PIK3R1,IGF-1(a PI3K/AKT activator)was added to PIK3R1-knockdown cells to observe its rescue effects on proliferation and apoptosis.Results Compared with healthy controls,PIK3R1 expression was significantly downregulated in PE placental tissues,accompanied by increased apoptosis,elevated Bax levels,and decreased Bcl-2,p-PI3K/PI3K,and p-AKT/AKT expression(P<0.05).PIK3R1 knockdown in HTR-8/SVneo cells suppressed proliferation,promoted apoptosis,and inhibited the PI3K/AKT pathway,whereas PIK3R1 overexpression had the opposite effect(P<0.05).Activation of PI3K/AKT by IGF-1 rescued the proliferation inhibition and apoptosis enhancement caused by PIK3R1 knockdown(P<0.05).Conclusion PIK3R1 inhibits placental trophoblast apoptosis and promotes proliferation by activating the PI3K/AKT signaling pathway.Its downregulation may contribute to the pathogenesis of PE.更多还原