[Effects of parthenolide on estradiol-synthesizing enzyme, ER isoforms and VEGF in human endometriotic stromal cells].

Objective: To evaluate the effects of parthenolide on estradiol-synthesizing enzyme, steroidogenic acute regulatory protein (StAR), and ER isoforms,VEGF in human endometriotic stromal cells. Methods: Primary endometriotic stromal cells were treated with different concentrations (1, 5, 10 and 20 μmol/L) of parthenolide. The mRNA of StAR, ER isoforms (ERα and ERβ), PR, vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumour necrosis factor-α (TNFα), tumour necrosis factor receptor (TNFR) 1, TNFR2 were measured by real-time PCR. The levels of estradiol and progesterone in the cell supernatant were measured by ELISA. Results: Different concentrations of parthenolide could up-regulate the mRNA of StAR in primary endometriotic stromal cells (F=5.722, P<0.05); the mRNA of StAR in the group of 20 μmol/L was significantly higher than that of the control group [2.6±0.3 versus 1.0, P<0.01]. Different concentrations of parthenolide could down-regulate the mRNA of ERα (F=6.921, P<0.01); the mRNA of ERα in the group of 20 μmol/L and 10 μmol/L were significantly lower than those of the control group [0.2±0.3 versus 0.3±0.3 versus 1.0, all P<0.05]. Different concentrations of parthenolide could down-regulate the ratios of ERα/ERβ mRNA levels (F=4.209, P<0.05). Different concentrations of parthenolide could up-regulate the mRNA of VEGF and TNFR1 (F=10.964, P<0.01; F=7.286, P<0.01). There were no statiscal significances with different concentrations of parthenolide on the mRNA of ERβ, PR, IL-6, TNFα and TNFR2, and the levels of estradiol and progesterone in the cell supernatant (all P>0.05). Conclusions: Parthenolide may regulate the expression of estradiol-synthesizing enzyme, ER isoforms and angiogenesis in endometriotic stromal cells. Parthenolide may promote the development of endometriosis.目的： 观察小白菊内酯对异位子宫内膜间质细胞雌激素合成相关酶——类固醇激素合成急性调节蛋白（StAR）、ER亚型、VEGF表达的影响。 方法： 原代培养异位子宫内膜间质细胞，再分别使用1、5、10、20 μmol/L 4组不同浓度的小白菊内酯刺激异位子宫内膜间质细胞，使用实时PCR技术检测StAR、ERα、ERβ、PR、血管内皮生长因子（VEGF）、白细胞介素6（IL-6）、肿瘤坏死因子α（TNFα）、肿瘤坏死因子受体（TNFR）1、TNFR2 mRNA的表达变化，应用ELISA方法检测细胞上清液中雌二醇、孕酮浓度的变化。 结果： 4组不同浓度的小白菊内酯刺激后，异位子宫内膜间质细胞中StAR mRNA的表达有上调（F=5.722，P<0.05），其中20 μmol/L组StAR mRNA的表达较对照组增高[分别为2.6±0.3和1.0]，两组比较，差异有统计学意义（P<0.01）；ERα mRNA的表达有下调（F=6.921，P<0.01），其中20 μmol/L组、10 μmol/L组ERα mRNA的表达较对照组显著降低[分别为0.2±0.3、0.3±0.3和1.0，P均<0.05]；ERα/ERβ mRNA比值显著下降（F=4.209，P<0.05）。4组不同浓度的小白菊内酯刺激后，异位子宫内膜间质细胞中VEGF mRNA的表达明显上调（F=10.964，P<0.01），其中20 μmol/L组VEGF mRNA的表达较1 μmol/L组、5 μmol/L组、10 μmol/L组、对照组均显著增高[分别为2.8±0.5、1.3±0.3、1.4±0.4、1.7±0.5和1.0，P均<0.05]；TNFR1 mRNA的表达明显上调（F=7.286，P0.05）。4组不同浓度的小白菊内酯刺激后，异位子宫内膜间质细胞上清液中雌二醇和孕酮的浓度无差异（F=3.376，P=0.054；F=0.932，P=0.483）。 结论： 小白菊内酯可能通过调控异位子宫内膜间质细胞中雌激素合成相关酶、ER亚型的表达及血管生成，促进子宫内膜异位症的病情进展。.