SRC—1對異位內膜雌激素調控的CXCL12表達的影響

[摘要] 目的 研究子宮內膜異位癥患者的異位內膜中類固醇激素受體輔活化子-1（SRC-1）和趨化因子配體12（CXCL12）的表達水平，從而了解SRC-1對異位子宮內膜雌激素（E2）調控的CXCL12表達的影響。方法 2014年9月—2016年9月，方便選擇在蘇州大學附屬第一醫院婦科因內異癥接受手術治療，術后標本證實為內異癥的15例患者的異位內膜及同期放置宮內節育器的無內異癥且月經周期正常的健康婦女10名的正常內膜，應用實時熒光定量RT-PCR方法比較正常子宮內膜和異位子宮內膜在月經的增生期和分泌期SRC-1和CXCL12mRNA表達水平。ELISA檢測沉默異位內膜SRC-1的表達對雌激素誘導異位內膜基質細胞表達CXCL12的影響。結果 正常子宮內膜基質細胞中SRC-1和CXCL12的表達呈現周期性變化，而異位內膜這兩種因子的表達并沒有周期性的改變。異位內膜SRC-1和CXCL12mRNA的表達與正常內膜相比明顯升高。沉默異位內膜SRC-1表達后，E2誘導的CXCL12表達下降50.04%（P<0.05）。 結論 類固醇激素受體輔活化子調控異位內膜表達CXCL12的作用中，SRC-1是雌激素的主要輔激活化子。

[關鍵詞] 甾體激素受體輔活化子-1；趨化因子配體12；子宮內膜異位癥

[中圖分類號] R737.9 [文獻標識碼] A [文章編號] 1674-0742（2016）12（c）-0034-03

[Abstract] Objective To observe the expression of steroid coactivator-1（SRC-1） and steroid-induced CXCL12 in endometriosis （EMS） and to explore the roles of SRC-1in the steroid-induced CXCL12 expression in EMS. Methods Convenient selection from September 2014 to September 2016，15 endometriosis cases undergoing surgery in The First Affiliated Hospital of Soochow University were enrolled in this study.Their ectopic endometriosis were from ovarian endometriomata which were identified pathologically. The 10 normal endometrium were acquired from the healthy women with normal cycle. Quantitative real-time polymerase chain reaction was used to quantify the mRNA levels of SRC-1 and CXCL12 during the menstrual cycle. ELISA was adopted to analyze the steroids-induced CXCL12 expression before and after the SRC-1 was silenced by siRNA. Results The SRC-1 and CXCL12 showed marked cyclic differences in normal endometrium. There were no periodic variation in the expression of SRC-1and CXCL12 in ectopic endometrium throughout the menstrual cycle. The SRC-1 and CXCL12 of ectopic endometrium were significantly higher than that of normal endometrium. Silencing of SRC-1 significantly reduced the E2-induced CXCL12 expression to 50.04%（P<0.05）. Conclusion SRC-1 is the major coactivator of E2-induced CXCL12 expression in EMS.

[Key words] Steroid receptor coactivator -1； Chemokine ligand 12； Endometriosis of uterus

趨化因子配體12（CXCL12）是趨化因子家族成員之一，它通過和受體CXCR4結合，激活MAPK信號通路，可以促進胚胎發育，血管形成以及腫瘤的生長和遠處轉移[1]。CXCL12是雌激素調節基因，雌激素（E2）可以使子宮內膜基質細胞中CXCL12的表達升高[2]。Ruiz等[3]實驗研究表明內異癥患者CXCL12和CXCR4呈現高表達。類固醇激素受體輔活化子-1（SRC-1）是SRCs家族成員之一[4]，它可以增強許多核受體的轉錄活性，包括雌激素受體和孕激素受體。……