Page 49 - 南京医科大学学报自然科学版

第41卷第8期 南京医科大学学报（自然科学版）
2021年8月 Journal of Nanjing Medical University（Natural Sciences） ·1151 ·

·基础医学·

子痫前期胎盘样本的多肽组学分析及差异多肽功能的初步探究

邵慧静，王天俊，张嘉嘉，杨娜娜 ，孙丽洲 *
*
南京医科大学第一附属医院产科，江苏 南京 210029

［摘 要］ 目的：通过液相色谱⁃串联质谱（LC⁃MS/MS）探索子痫前期胎盘样本中的多肽表达，并对其中差异多肽的体外功能
进行初步探究。方法：收集2019年5—9月在南京医科大学第一附属医院产科行计划性剖宫产手术的4例正常足月孕妇胎盘
和4例子痫前期孕妇胎盘组织。利用超滤法、LC⁃MS/MS检测样本中多肽的表达水平差异。通过CCK⁃8法，克隆形成实验以及
Transwell实验初步研究差异多肽 SPLFMGKVVNPTQK 对滋养细胞（HTR⁃8/SVneo）增殖、迁移能力的影响。脐静脉内皮细胞
405
418
（HUVECs）成管实验初步研究该多肽对HUVECs细胞血管形成能力的影响。使用qPCR和Western blot检测多肽处理组与对照
组中的金属蛋白质酶MMP2以及金属蛋白酶组织抑制剂（TIMP1）的表达。结果：共鉴定到3 582条多肽片段，48条差异表达多
肽。体外功能实验表明，差异多肽 SPLFMGKVVNPTQK 能够促进滋养细胞增殖迁移以及内皮细胞的管状形成能力。多肽处
405
418
405
理后MMP2表达明显上调，TIMP1的表达明显下调。结论：子痫前期胎盘与正常胎盘间存在差异多肽，且差异多肽 SPLFMGKV⁃
VNPTQK 能够促进滋养细胞以及内皮细胞的功能，为子痫前期发病机制研究以及治疗提供了多肽组学的支持。
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［关键词］ 子痫前期；多肽组学；内源性多肽；滋养细胞
［中图分类号］ R714.245 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）08⁃1151⁃09
doi：10.7655/NYDXBNS20210807

Comparative peptidome analysis of preeclamptic placenta and functional study of the

differential peptides
* *
SHAO Huijing，WANG Tianjun，ZHANG Jiajia，YANG Nana ，SUN Lizhou
Department of Obstetrics and Gynecology，the First Affiliated Hospital of Nanjing Medical University，Nanjing
210029，China

［Abstract］ Objective：This study aims to identify the peptide with different expression in preeclamptic placenta by liquid
chromatography⁃tandem mass spectrometry（LC⁃MS/MS），and to study the bio⁃active function of the differentially expressed peptides.
Methods：Placental tissues were collected from 4 normal pregnant women and 4 pregnant women with preeclampsia. All participants
underwent planned cesarean section in the Department of Obstetrics，the First Affiliated Hospital of Nanjing Medical University from
May 2019 to September 2019. The effects of the differential peptide 405 SPLFMGKVVNPTQK 418 on the proliferation and migration of
trophoblast cells（HTR⁃8/SVneo）were studied by CCK⁃8 assay，clone formation assay and transwell assay. And the matrigel assay was
used to study the effect of this peptide on the angiogenesis ability of human umbilical vein endothelial cells（HUVECs）. Western blot
was used to detect the metalloproteinase 2（MMP2）and metalloproteinase tissue inhibitor 1（TIMP1）in peptide⁃treated group and
control group. Results：A total of 3 582 peptides were screened out and 48 differentially expressed peptides were identified. In vitro
functional assays showed that the differential peptide 405 SPLFMGKVVNPTQK 418 could promote the proliferation and migration of
trophoblast cells and the tube formation ability of endothelial cells. After peptide treatment，the expression of MMP2 was up⁃regulated
and the expression of TIMP1 was down ⁃ regulated. Conclusion：A series of differentially expressed peptides were detected in
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preeclamptic placenta，and the differential peptide 405 SPLFMGKVVNPTQK exhibited a promotive role in the behaviour of trophoblast
cells and endothelial cells，which provides support for the study of pathogenesis and treatment of preeclampsia.
［Key words］ preeclampsia；peptidomics；endogenous peptide；trophoblast cell
［J Nanjing Med Univ，2021，41（08）：1151⁃1159］
［基金项目］ 国家重点研发计划（2018YFC1002205）；国家自然科学基金面上项目（81771603）；江苏省妇幼健康科学研究项目
（FRC201755）
∗
通信作者（Corresponding author），E⁃mail：lizhou_sun@163.com；nanayang210@163.com