药物治疗对子宫内膜异位症患者在位内膜凋亡的影响

Effects of Medical Treatment on Apoptosis in Eutopic Endometrium of Patients with Endometriosis

目的探讨药物治疗,包括左炔诺孕酮宫内节育系统(LNG-IUS)、口服甲羟孕酮(MPA)或注射促性腺激素释放激素类似物(GnRHa)对子宫内膜异位症患者在位内膜凋亡的的影响。方法采集中、重度子宫内膜异位症患者术前以及放置LNG-IUS、口服MPA或注射GnRHa后的在位内膜,以末端转移酶介导的缺口末端标记法(TUNEL)检测细胞凋亡率,透射电镜观察细胞形态,RT-PCR检测内膜中凋亡相关蛋白Bax、Fas和Fas-LmRNA的表达。结果放置LNG-IUS后,在位内膜腺体细胞凋亡率由(24.4±35.0)%升高至(51.0±37.8)%(P=0.027),间质细胞凋亡率由(35.3±30.2)%升高至(76.4±11.2)%(P=0.008)。电镜下的凋亡状况,按程度由强至弱依次为:注射Gn-RHa、放置LNG-IUS、口服MPA。子宫内膜异位症患者在位内膜中Fas-LmRNA的表达率显著高于正常对照(P<0.05),但药物治疗前后3种凋亡相关蛋白mRNA的表达差异均无显著性。结论药物治疗可促进在位内膜凋亡,其诱导内膜细胞凋亡的作用由强至弱依次为:注射GnRHa、放置LNG-IUS、口服MPA。

Objective To investigate the apoptosis-related mechanisms of levenorgestrel-releasing intrauterine system （LNG-IUS） , oral medroxyprogesterone （MPA）, and injective gonadotrophic hormone releasing hormone agonist （GnRHa） on eutopic endometrium of patients with endometriosis. Methods We collected the samples of endometrium from patients with endometriosis before operation and after insertion of LNG-IUS, administration of oral MPA, or injection of GnRHa. The uhrastructure of endometria was observed and compared by electron microscopy. Apoptotic cells were assessed by the terminal deoxynucleotidyl transferasemediated deoxy-UTP nick-end labeling （TUNEL） assay, and the expressions of Bax, Fas, and Fas-L mRNA were determined by semi-quantitative reverse transcription-polymerase chain raction. Results After have been exposured to LNG-IUS, the apoptotic rate of endometrial epithelial cells and stromal cells increased from （24. 4 ± 35.0）% to （51.0±37.8）% （P=0.027） and （35.3 ±30.2）% to （76.4±11.2）% （P=0. 008）, re- spectively. The degree of apoptosis under transmission electron microscopy was in an order of GnRHa 〉 LNG- IUS 〉 MPA. The expression of Fas-L mRNA in eutopic endometrium of patients with endometriosis was significantly higher than that of the normal control （ P 〈 0.05 ）. The expressions of three apoptosis-related proteins had no significant difference. Conclusion Medical treatments can increase the apoptosis of eutopic endometrial cells, and such effect was strongest in GnRHa and relatively weaker in LNG-IUS and MPA.