孕期暴露DEHP对大鼠胎盘雌激素合成酶及基质金属蛋白酶基因表达的影响及PPARG在其中的作用

黄玉晶; 陈济安; 谭瑶; 邱志群; 罗教华; 曾惠; 舒为群

doi:10.13421/j.cnki.hjwsxzz.2016.05.001

孕期暴露DEHP对大鼠胎盘雌激素合成酶及基质金属蛋白酶基因表达的影响及PPARG在其中的作用

Effects Of DEHP on Expression of Estrogen Synthetase and Matrix Metalloproteinases in Placenta: Possible Involvement of PPARG

摘要

摘要:
目的通过动物实验研究孕期暴露邻苯二甲酸（2-乙基己基）酯（DEHP）对大鼠胎盘过氧化物酶体增殖物激活受体G（PPARG）表达的影响及其在DEHP调控基因表达中的作用。
方法 6周-7周龄健康雌性SD大鼠60只，随机分为3组，每天灌胃染毒：溶剂对照组（玉米油），染毒组（DEHP 2 g/kg）和干预组（DEHP 2 g/kg，染毒第28天起加入PPARG拮抗剂GW 992 0.5 mg/kg），染毒第30天起与健康成年SD雄性大鼠合笼，妊娠第20天处理取胎盘，western-blot测PPARG蛋白表达，实时定量PCR测PPARG、激素合成关键酶（CYP191、17HSDb1、17HSDb2、17HSDb3、17HSDb4、17HSDb7、17HSDb8、3HSDb1）、前列腺素E2合成代谢关键酶（PLA2G4A、PTGS2、PTGES2、HPGD）、基质金属蛋白酶（MMP2、MMP9）mRNA表达。
结果胎盘PPARG在染毒组和干预组蛋白表达显著升高（与对照比P < 0.01），mRNA表达未见显著改变（P>0.05）。染毒组胎盘17HSDb3、17HSDb4、17HSDb7和3HSDb1表达显著高于对照组（P < 0.01），CYP191a1，MMP2和MMP9表达低于对照组（P < 0.01）。其中17HSDb3、17HSDb4、MMP9表达在干预组显著回复（17HSDb3与染毒组比P < 0.01，17HSDb4、MMP9与对照组比P>0.05）。
结论孕期暴露DEHP可上调大鼠胎盘PPARG蛋白表达，从而调节胎盘部分雌激素合成关键酶及基质金属蛋白酶mRNA表达，这可能是DEHP阻碍孕期胎盘雌激素和基质金属蛋白酶的合成分泌的途径之一。

Abstract:
Objectives To understand the role of peroxisome proliferator activated receptors gamma (PPARG) in the effects of di (2-ethylhexyl) phthalate exposure on regulation of estrogens and inflammatory mediators in placeta.
Method A total of 60 female Sprague-Dawley rats (6-7 weeks old) were randomly divided into 3 groups, 20 in each, control group (corn oil), exposure group (2 g/kg of DEHP), intervention group (DEHP 2 g/kg, and 0.5 mg/kg GW9662 (antagonist of PPARG) were added from 28^th day), the treatments were conducted through gavage everyday. The female rats were mated with health male rats at 30th day of treatment and sacrificed at day 20 of gestation. The placenta were isolated for the detection of PPARG protein and PPARG, CYP191, 17HSDb1, 17HSDb2, 17HSDb3, 17HSDb4, 17HSDb7, 17HSDb8, 3HSDb1, PLA2G4A, PTGS2, PTGES2, HPGD, MMP2, MMP9 mRNA expression.
Results Compared with the control, the protein expression of PPARG in placenta significantly increased in both exposure and intervention group (P < 0.01). The mRNA expression of 17HSDb3, 17HSDb4, 17HSDb7 and 3HSDb1, significantly increased in exposure group (P < 0.01), CYP191a1, MMP2 and MMP9 significantly decreased in exposure group (P < 0.01).The mRNA expression of 17HSDb3、17HSDb4、MMP9 was recuperated significantly in intervention group.
Conclusion The present study shows that DEHP exposure in pregnancy can disturb estrogens and matrix matalloproteinases synthesis in placenta, which is partially associated with the up-regulation of placenta PPARG expression.

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