miR‑15a‑5p对子痫前期胎盘滋养细胞自噬的影响  

Effect of miR-15a-5p on autophagy of placental trophoblasts in preeclampsia

作　　者：于素美 张玉月 马丽文 况园军 常庆宁 孔敏 张慧萍 YU Sumei;ZHANG Yuyue;MA Liwen;KUANG Yuanjun;CHANG Qingning;KONG Min;ZHANG Huiping(Clinical Medical College,Ningxia Medical University,Yinchuan 750004,China;National Health Commission Key Laboratory of Metabolic Cardiovascular Disease Research,Yinchuan 750004,China;General Hospital of Ningxia Medical University,Ningxia 750004,China;不详)

机构地区：[1]宁夏医科大学临床医学院,银川750004 [2]国家卫生健康委代谢性心血管疾病研究重点实验室,银川750004 [3]宁夏医科大学总医院,银川750004 [4]湖南省妇幼保健院,长沙410008

出　　处：《实用医学杂志》2024年第12期1631-1636,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:82171682);中国医学科学院中央级公益性科研院所基本科研业务费项目(编号:2019PT330002);宁夏医科大学校级科研项目重点项目(编号:XZ202200);宁夏回族自治区重点研发计划重点项目(编号:2022BEG02054,2021BEG02028,2019BFG02004)。

摘　　要：目的探讨miR‑15a‑5p对子痫前期胎盘滋养细胞自噬的影响。方法收集2020年12月至2022年12月的正常妊娠胎盘组织和子痫前期胎盘组织各20例。采用荧光定量PCR检测胎盘组织和滋养细胞中miR‑15a‑5p的表达,并对其表达水平与患者血压做相关性分析;将HTR8‑S/Vneo细胞分正常组(control)和缺氧组(hypoxia),观察缺氧对miR‑15a‑5p表达的影响。另设mimic‑NC组、mimic‑NC+hypoxia组、miR‑15a‑5p mimic组、miR‑15a‑5p mimic+hypoxia、inhibitor‑NC组、inhibitor‑NC+hypoxia、miR‑15a‑5p inhibitor组、miR‑15a‑5p inhibitor+hypoxia组,观察miR‑15a‑5p对缺氧诱导的滋养细胞自噬相关蛋白LC3B和p62蛋白的影响。用Western blot检测各组中自噬相关蛋白LC3B和p62蛋白的表达水平;TargetScan网站预测miR‑15a‑5p的靶基因,检测其在胎盘组织和滋养细胞中的表达水平。结果与对照组相比,miR‑15a‑5p在子痫前期胎盘组织和缺氧滋养细胞中的表达均增高,且与患者血压呈正相关;缺氧条件下过表达miR‑15a‑5p,LC3BⅡ/Ⅰ表达增高,P62蛋白相对表达量降低;干扰miR‑15a‑5p后,LC3BⅡ/Ⅰ表达量降低,p62蛋白表达量升高;荧光定量PCR及Western blot检测结果发现YAP1在子痫前期胎盘组织和缺氧滋养细胞中的表达水平明显降低。结论miR‑15a‑5p在子痫前期胎盘滋养细胞中的高表达,其可能通过与YAP1结合从而促进PE自噬的发生。Objective Investigating the impact of miR-15a-5p on autophagy in trophoblast cells of preeclamptic placenta.Methods Collect 20 cases of normal placental tissue and 20 cases of preeclamptic placental tissue from December 2020 to December 2022.Use fluorescence quantitative PCR to detect the expression of miR-15a-5p in placental tissue and trophoblast cells,and study its correlation with patient blood pressure.The HTR8-S/Vneo cells are divided into normal group(control)and hypoxia group,and the effect of hypoxia on the expression of miR-15a-5p is observed.Additionally,mimic-NC group,mimic-NC+hypoxia group,miR-15a-5p mimic group,miR-15a-5p mimic+hypoxia group,inhibitor-NC group,inhibitor-NC+hypoxia group,miR-15a-5p inhibitor group,and miR-15a-5p inhibitor+hypoxia groups are set up to observe the effect of miR-15a-5p on hypoxiainduced autophagy-related proteins LC3B and p62 protein in trophoblast cells.Western blot is used to detect the expression levels of autophagy-related proteins LC3B and p62 protein in each group;TargetScan website predicts the target genes of miR-15a-5p,and detects their expression levels in placental tissue and trophoblast cells.Results Compared with the control group,the expression levels of miR-15a-5p were significantly increased in the placentas and hypoxic trophoblasts of preeclampsia,and they were positively correlated with the blood pressure of the patients.Under hypoxic conditions,the overexpressed miR-15a-5p promoted the protein expression of LC3BII/I,while the relative expression of P62 was decreased.But after interference with miR-15a-5p,LC3BII/I expression was downregulated and P62 expression was up-regulated.The results of quantitative PCR and Western blot showed that the expression levels of YAP1 in the preeclampsia placental tissues and hypoxic trophoblasts were significantly reduced.Conclusion The upregulation of miR-15a-5p in trophoblast cells of the placenta in individuals with preeclampsia could enhance autophagy in preeclampsia by forming a complex with YAP1.

关 键 词：子痫前期 滋养细胞 自噬 miR‑15a‑5p YAP1 

分 类 号：R714.25[医药卫生—妇产科学]