国际生殖健康/计划生育杂志

国际生殖健康/计划生育 ›› 2016, Vol. 35 ›› Issue (5): 357-361.

• 论著 •    下一篇

PM2.5对人绒毛膜外滋养层细胞HTR8-SVneo迁移与侵袭力的影响及机制研究

秦喆，侯海燕，徐忠伟，张立文，韩斌，陈亚琼，吴思雨，姚婷   

  1. 300162 天津，中国人民武装警察部队后勤学院附属医院妇产科（秦喆，侯海燕，陈亚琼，吴思雨，姚婷）；中国医学科学院北京协和医学院（侯海燕）；中国人民武装警察部队后勤学院中心实验室（徐忠伟）；天津医科大学公共卫生学院（张立文）；中国环境科学研究院环境基准与风险评估国家重点实验室（韩斌）
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2016-10-25 发布日期:2016-10-25
  • 通讯作者: 陈亚琼

Effect of PM2.5 on Migration and Invasion of Human Chorionic Trophoblast Cells and its Mechanism

QIN Zhe, HOU Hai-yan，XU Zhong-wei，ZHANG Li-wen，HAN Bin，CHEN Ya-qiong，WU Si-yu，YAO Ting   

  1. Department of Obstetrics and Gynecology，Affiliated Hospital of Logistics University of Chinese People′s Armed Police Forces，Tianjin 300162，China （QIN Zhe， HOU Hai-yan，CHEN Ya-qiong，WU Si-yu，YAO Ting）；Peking Union Medical College Hospital，China Academy of Sciences，Beijing 100730，China（ＨＯＵ Ｈａｉ－ｙａｎ）；Ｃentral Laboratory，Logistics University of Chinese People′s Armed Police Forces，Tianjin 300162，China （ＸＵ Ｚｈｏｎｇ－Ｗｅｉ）；Ｓｃｈｏｏｌ ｏｆ Ｐｕｂｌｉｃ Ｈｅａｌｔｈ，Ｔｉａｎｊｉｎ Ｍｅｄｉｃａｌ Ｕｎｉｖｅｒｓｉｔｙ，Ｔｉａｎｊｉｎ ３０００７０，Ｃｈｉｎａ（ＺＨＡＮＧ Ｌｉ－ｗｅｎ）；Ｓｔａｔｅ Ｋｅｙ Ｌａｂｏｒａｔｏｒｙ ｏｆ Ｅｎｖｉｒｏｎｍｅｎｔａｌ Ｃｒｉｔｅｒｉａ ａｎｄ Ｒｉｓｋ Ａｓｓｅｓｓｍｅｎｔ，Ｃｈｉｎｅｓｅ Ｒｅｓｅａｒｃｈ Ａｃａｄｅｍｙ ｏｆ Ｅｎｖｉｒｏｎｍｅｎｔａｌ Ｓｃｉｅｎｃes，Beijing 100012，Chiｎａ （ＨＡＮ Ｂｉｎ）
  • Received:1900-01-01 Revised:1900-01-01 Published:2016-10-25 Online:2016-10-25
  • Contact: CHEN Ya-qiong

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摘要： 目的：探讨PM2.5对人绒毛膜外滋养细胞HTR8-SVneo存活率以及迁移与侵袭能力的影响，寻找PM2.5致不良妊娠结局可能的机制。方法：不同浓度PM2.5染毒HTR8-SVneo细胞建立实验模型，CCK8（Cell Counting Kit-8）法分析细胞增殖情况，最终选取0、30、60、120和200 μg/mL 5个浓度进行后续实验，其中以0 μg/mL染毒组为对照组。激光全息细胞分析及成像系统分析细胞迁移力；Transwell侵袭实验分析细胞侵袭力；qPCR和Western Blot分别检测基质金属蛋白酶2（MMP2）、MMP9及其组织抑制剂TIMP1、TIMP2的mRNA和蛋白表达水平；明胶酶谱法检测细胞分泌的明胶酶MMP2和MMP9活性。结果：PM2.5对HTR8-SVneo细胞增殖有显著抑制作用（P＜0.05）；PM2.5使HTR8-SVneo细胞迁移距离和穿膜细胞数均减少（P＜0.05）；qPCR和Western Blot结果显示，PM2.5使HTR8-SVneo细胞MMP2、MMP9、TIMP1及TIMP2的mRNA及蛋白表达水平升高（Ｐ＜0.0５）， 且MMPs升高程度低于TIMPs；明胶酶谱结果显示，HTR8-SVneo细胞MMP9活性在30、60、120和200 μg/mL染毒组均升高（P＜0.05）。结论：PM2.5在造成HTR8-SVneo细胞损伤的同时，可能通过打破MMPs/TIMPs的动态平衡影响人绒毛膜外滋养细胞HTR8-SVneo的迁移与侵袭力，从而造成不良妊娠结局，而具体信号机制有待深入研究。

关键词: 空气污染物, 滋养层, 细胞迁移分析, 基质金属蛋白酶2, 基质金属蛋白酶9, 金属蛋白酶1组织抑制剂, 金属蛋白酶2组织抑制剂

Abstract: Objective: To investigate the effect of PM2.5 on the survival rate, the migration ability and the invasion ability of human chorionic trophoblast cell line, HTR8-SVneo, and to explore the possible mechanism of the adverse pregnancy outcome induced by PM2.5. Methods：The in vitro cultured HTR8-SVneo cells were treated with PM2.5. The cell proliferation was analysed by CCK8. Five concentrations of 0, 30, 60, 120 and 200 μg/mL were selected. The cell migration was detected by Laser holographic cell analysis and imaging system, while the cell invasion by the Transwell experiment. The mRNA and protein expressions of MMP2, MMP9, TIMP1 and TIMP2 were measured by qPCR and Western Blot, while the activities of MMP2 and MMP9 by a gelatin zymography. Results：The proliferation of HTR8-SVneo cells was significantly inhibited by PM2.5 treatment (P＜0.05), while the migration distance and the number of cells penetrating the membrane were decreased (P＜0.05). The mRNA and protein expressions of MMP2, MMP9, TIMP1 and TIMP2 were significantly increased in PM2.5 exposed groups(P＜0.05), and the increased degree of MMPs was lower than TIMPs. The activities of MMP9 in all PM2.5 treatment groups were significantly increased when compared with the control group (P＜0.05). Conclusions：PM2.5 can induce the cellular damage of HTR8-SVneo cells, while PM2.5 can decrease the cell migration and invasion by inducing the imbalance between MMPs and TIMPs. These pathophysiological changes are related with the adverse pregnancy outcomes.

Key words: Air pollutants, Trophoblasts, Cell migration assays, Matrix metalloproteinase 2, Matrix metalloproteinase 9, Tissue inhibitor of metalloproteinase-1, Tissue inhibitor of metalloproteinase-2