促性腺激素释放激素激动剂对子宫腺肌病在位内膜细胞凋亡的影响

Effect of gonadotropin releasing hormone analogues on apoptosis of cultured adenomyosis endometrial cells

目的研究促性腺激素释放激素激动剂（GnRHa）对子宫腺肌病（AM）在位内膜细胞凋亡的影响。方法取本院妇科住院行全子宫切除术的32例AM患者在位子宫内膜细胞为研究组；同期因卵巢上皮性良性肿瘤行卵巢囊肿剔除术的20例患者正常子宫内膜细胞为对照组。两组细胞进行体外培养，用GnRHa10^-7、10^-5mol／L分别作用24、48、72h后，用末端转移酶介导的缺口末端标记法（TUNEL）及流式细胞仪检测各组细胞的凋亡率。结果（1）镜下可见两组部分细胞固缩、漂浮、核浓缩、碎裂，呈典型的凋亡小体；（2）不含GnRHa培养的AM在位内膜细胞凋亡率在各时间点均低于对照组，且两组都随时间的延长凋亡率增加（P〈0．01）；（3）GnRHa作用后，两组的凋亡率高于作用前，且均随浓度的增加而增加，且研究组各时间点、各浓度AM在位内膜细胞凋亡率均显著高于同时间、同浓度的对照组（P〈0．01）。结论在位内膜细胞凋亡率异常可能是AM发病机制之一。GnRHa可能以自分泌或旁分泌机制直接作用于子宫在位内膜细胞，提高了AM在位内膜细胞的凋亡率。

Objective To investigate the effects of gonadotropin releasing hormone analogues （GnRHa） on apoptosis of cultured adenomyosis （AM） endometrial cells. Methods Eutopic endometrial cells from 32 women who received hysterectomy for AM （ study group） and 20 women who received ovarian cyst surgery for benign ovarian epithelial tumor （ control group） of gynaecology department in our hospital were cultured in vitro. Apoptotic ratio was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） and flow cytometry before and after using GnRHa（ 10^ -7 mol/L, 10 ^-5 mol/L for 24 h, 48 h,72h）. Results （1）Cells in two groups showed cell shrinkage, floating, nucleus concentration, nuclear fragmentation and typical apoptotic bodies. （ 2 ） The apoptotic ratio of cultured AM endometrial cell without GnRHa was lower than that in control group and the apoptotic ratio increased with the prolongation of time in two groups （ P 〈 0.01 ）. （ 3 ） After GnRHa addition, each group showed higher apoptotic ratio and a trend towards higher apoptotic ratio linked to advanced concentration. Furthermore, apoptotie ratio in study group was significantly higher than that in control group at the same time point and same concentration（ P 〈 0.01 ）. Conclusions The abnormality of apoptotic ratio of AM endometrial cells may be associated with the AM pathogenesis. GnRHa may increase the apoptotic ratio of cultured AM endometrial cells by autocrine or paracrine.