过氧化物酶体增殖物激活受体γ及其配体对早孕期绒毛组织及细胞滋养细胞浸润能力的影响  

Effect of peroxisome proliferators-activated receptor γ ligands on cytotrophoblast invasion in first trimester pregnancy

作　　者：李淑娟[1] 尚涛[1] 常子强[2] 李俊[1] 李思扬[1] 李秋玲[1] 芮广海[1] 

机构地区：[1]沈阳中国医科大学附属第二医院妇产科,110004 [2]北京顺义医院妇产科

出　　处：《中华妇产科杂志》2007年第8期518-522,共5页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)及其配体对早孕期绒毛组织及细胞滋养细胞浸润能力的影响。方法采用免疫组化方法、免疫荧光细胞化学染色法、蛋白印迹法和RT-PCR 技术检测20例孕6～8周(早孕早期组)及20例孕11～12周(早孕晚期组)绒毛组织及细胞滋养细胞中的 PPARγ蛋白及其 mRNA 的表达;并检测不同浓度 PPARγ激动配体——15-脱氧-前列腺素 J_2(15-d-PGJ_2)和曲格列酮,以及不同浓度拮抗配体——双酚丙烷二环氧甘油醚(BADGE)对原代无血清培养的细胞滋养细胞浸润能力的影响。结果 (1)PPARγ蛋白在早孕早期组和早孕晚期组绒毛组织中均有表达,主要定位在细胞滋养细胞核中,合体滋养细胞及绒毛问质细胞中无表达。(2)早孕早期组绒毛组织和培养的细胞滋养细胞中,PPARγ蛋白表达水平分别为1.35±0.08、1.13±0.11,PPARγ mRNA 表达水平分别为36.0±5.1、13.4±3.1;早孕晚期组绒毛组织和培养的细胞滋养细胞中,PPARγ蛋白表达水平分别为1.17±0.03、0.86±0.05,PPARγ mRNA 表达水平分别为23.3±5.5、6.1±1.3,早孕晚期组 PPARγ蛋白及其 mRNA 表达水平明显低于早孕早期组,两组分别比较,差异均有统计学意义(P<0.05)。(3)PPARγ激动配体15-d-PGJ_2和曲格列酮均有抑制细胞滋养细胞的浸润的作用。15-d-PGJ_2浓度为1、10μmoL/L,曲格列酮浓度为10μmoL/L 时,早孕早期组细胞滋养细胞浸润指数分别为0.57±0.03、0.43±0.02、0.50±0.06,早孕晚期组分别为0.69±0.02、0.59±0.03、0.66±0.05,两组分别比较,差异均有统计学意义(P<0.05)。(4)PPARγ拮抗配体 BADGE 浓度为20、50μmol/L 时,早孕早期组细胞滋养细胞浸润指数分别为1.23±0.07和1.58±0.04;早孕晚期组分别为1.05±0.03和1.38±0.08,两组分别比较,差异均有统计学意义(P<0.05)。结论 PPARγ在调节滋养细胞浸润过程中起重要作用;在早孕期胎盘绒毛组织,PPARγ激动配体可抑制滋养细胞Objective To investigate the expression of peroxisome proliferators-activated receptor γ （PPARγ） in trophoblast and relation between PPARγ ligands and trophoblast invasion. Methods We examined the expression of PPARγ by immunohistochemistry, immunocytochemistry and real time quantitative PCR. We next examined, using the cytotrophoblast culture model, the biological role of PPARγ ligands in vitro. Results PPARγ was mainly localized in the nuclei of villous cytotrophoblast and extravillous cytotrophoblast of cell islands and cell columns. In villous tissue and cultured trophoblast from early first trimester, the level of expression of PPARγmRNA and protein was 36. 0±5. 1, 13.4±3. 1 and 1.35 ±0. 08, 1.13 ±0. 11 ; from late first trimester it was 23.3 ±5.5, 6. 1 ± 1.3 and 1.17 ±0. 03, 0. 86 ±0. 05, and the expression of PPARγ was obviously decreased （P 〈0. 05）. Our studies showed that both natural and synthetic PPARγ agonists inhibited cytotrophoblast invasion in a concentration-dependent manner. In trophoblast from early and late first trimester, while 15-d-PGJ2 at concentrations 1 and 10 μmol/L, troglitazone at a concentration 10 μmol/L, invasion index was 0.57 ± 0. 03, 0. 43 ± 0. 02, 0. 50 ± 0. 06 and 0. 69 ± 0. 02, 0. 59 ± 0. 03, 0. 66 ± 0.05. The effect on inhibition of trophoblast was significant compared with control （ P 〈 0.05 ） . Conversely, PPARγ antagonists promoted cytotrophoblast invasion. Furthermore the PPARγ antagonist abolished inhibitory effect of the PPARγ agonists partially. PPARγ ligands had a significant effect on cytotrophoblast from early first trimester more than cytotrophoblast from late first trimester（ P 〈 0. 05 ）. Conclusions PPARγ plays an important role in the modulation of trophoblast invasion. Consequently, one can hypothesize that abnormal increases in the production of PPARγ agonist ligands in placenta can alter trophoblast invasion and generate human pregnancy diseases such as preeclampsia.

关 键 词：滋养层 转录因子 受体 胞质和核 色满类 噻唑类 前列腺素D2 

分 类 号：R714[医药卫生—妇产科学]