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邻苯二甲酸酯对人子宫肌层和平滑肌瘤细胞的体外作用以及子宫肌瘤女性尿中邻苯二甲酸酯代谢物水平的升高。

In vitro effects of phthalate esters in human myometrial and leiomyoma cells and increased urinary level of phthalate metabolite in women with uterine leiomyoma.

作者信息

Kim Jin Hee, Kim Sung Hoon, Oh Young Sang, Ihm Hyo Jin, Chae Hee Dong, Kim Chung-Hoon, Kang Byung Moon

机构信息

Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

出版信息

Fertil Steril. 2017 Apr;107(4):1061-1069.e1. doi: 10.1016/j.fertnstert.2017.01.015. Epub 2017 Mar 11.

Abstract

OBJECTIVE

To investigate the possible role of phthalate, a ubiquitous chemical used in consumer products, in the pathogenesis of uterine leiomyoma.

DESIGN

Experimental and prospective case-control study using human samples.

SETTING

University hospital.

PATIENT(S): Fifty-three women with histologic evidence of uterine leiomyoma and 33 surgical controls without leiomyoma.

INTERVENTION(S): Human myometrial and leiomyoma cells were treated with di-(2-thylhexyl)-phthalate (DEHP).

MAIN OUTCOME MEASURE(S): Cell viability assay and Western blot analyses after in vitro DEHP treatment; high-performance liquid chromatography electrospray ionization tandem mass spectrometry in cases and controls.

RESULT(S): In vitro treatment with DEHP led to an increased viability and increased expressions of proliferating cell nuclear antigen, B-cell lymphoma 2 protein, and type I collagen in myometrial and leiomyoma cells. The urinary concentration of mono-(2-ethyl-5-carboxypentyl) phthalate was higher in women with leiomyoma compared with controls.

CONCLUSION(S): These findings suggest that exposure to phthalate may play a role in the pathogenesis of uterine leiomyoma by enhancing proliferative activity, exerting an antiapoptotic effect, and increasing collagen contents in myometrial and leiomyoma cells.

摘要

目的

研究邻苯二甲酸酯(一种广泛用于消费品的化学物质)在子宫平滑肌瘤发病机制中可能发挥的作用。

设计

使用人体样本进行的实验性前瞻性病例对照研究。

地点

大学医院。

患者

53名有子宫平滑肌瘤组织学证据的女性和33名无平滑肌瘤的手术对照者。

干预措施

用邻苯二甲酸二(2-乙基己基)酯(DEHP)处理人子宫肌层和平滑肌瘤细胞。

主要观察指标

体外DEHP处理后的细胞活力测定和蛋白质免疫印迹分析;病例组和对照组的高效液相色谱电喷雾电离串联质谱分析。

结果

DEHP体外处理导致子宫肌层和平滑肌瘤细胞活力增加,增殖细胞核抗原、B细胞淋巴瘤2蛋白和I型胶原表达增加。与对照组相比,平滑肌瘤女性尿中邻苯二甲酸单(2-乙基-5-羧基戊基)酯浓度更高。

结论

这些发现表明,接触邻苯二甲酸酯可能通过增强增殖活性、发挥抗凋亡作用以及增加子宫肌层和平滑肌瘤细胞中的胶原蛋白含量,在子宫平滑肌瘤的发病机制中发挥作用。

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