促性腺激素释放激素激动剂对子宫腺肌病在位子宫内膜细胞凋亡的影响
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摘要
目的:
1.研究促性腺激素释放激素激动剂(gonadotropin releasing hormone analogues, GnRHa)对子宫腺肌病(adenomyosis,AM)在位内膜细胞凋亡的影响。
2.探讨AM在位内膜细胞凋亡异常与AM发病机制的关系,为临床治疗提供新的思路及实验依据。
材料与方法:
1.研究对象
收集2007年10月至2008年7月广州医学院附属广州市第一人民医院妇科住院临床诊断为AM行全子宫切除术的患者32例,术后行病理检查确诊,取其在位内膜为研究组。患者年龄34～50岁,平均44.32岁。
收集同期因卵巢上皮性良性肿瘤行卵巢囊肿剔除术患者共20例,术前患者知情同意情况下行诊刮术留取内膜标本,作为对照组。术后病理证实诊断为正常子宫内膜。患者年龄32～46岁,平均42.30岁。
研究组及对照组患者均月经周期规则,术前三个月内未服用过激素类药物,无其他内分泌、免疫和代谢疾病。
2.实验方法
对研究组及对照组子宫内膜细胞为对照组进行体外培养,免疫组化鉴定细胞类型,确定为子宫内膜细胞后用GnRHa 10-7 mol/L、10-5 mol/L两种药物浓度分别作用24、48、72 h三个时间点后用脱氧核苷酸末端转移酶介导的缺口末端标记技术(TdT-mediated biotinylated dUTP nick end labeling,TUNEL)及流式细胞仪AnnexinV-FITC/PI方法检测各组细胞的凋亡率。
3.统计学分析
本研究结果采用SPSS13.0统计软件处理,组间比较用单因素方差分析,方差齐者用LSD-t法,方差不齐者用Dunnett-t法。以P<0.05为差异有统计学意义。
结果:
1. GnRHa作用前AM在位内膜细胞各时间点凋亡率均明显低于正常子宫内膜细胞(P<0.01)。
2. GnRHa作用后各时间点AM在位内膜细胞及正常子宫内膜细胞凋亡率均随作用时间增长明显增加(P<0.01);AM在位内膜细胞凋亡率增加程度显著高于正常子宫内膜细胞(P<0.01)。
结论:
1.AM在位内膜细胞凋亡率异常可能是AM发病机制之一。
2. GnRHa作用后子宫内膜细胞凋亡率较作用前明显增高,表明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,成为GnRHa局部治疗的实验依据。
3. GnRHa作用后两组子宫内膜细胞的凋亡率高于作用前,且随作用时间、浓度的增加而增加,提示在一定作用时间和剂量范围内,GnRHa与子宫内膜细胞的凋亡率具有时间和剂量依赖性。
Objective
1. To investigate the effects of gonadotropin releasing hormone analogues (GnRHa) on apoptosis of cultured adenomyosis(AM) endometrial cells.
2. To determine the roles of abnormality of apoptosis of AM endometrial cell in the pathogenesis of adenomyosis and provide new approach and experimental evidences for the clinical treatment of adenomyosis.
Materials and methods
1. Samples
Eutopic endometrial cells from 32 women who received hysterectomy for AM(study group) and 20 women who received ovarian cyst surgery for benigh ovarian epithelial tumor(control group) of gynaecology department in our hospital were cultrued in vitro.
2. Methods
Detect the apoptotic ratio by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and flow cytometry(AnnexinV-FITC/PI) before and after using GnRHa.
3. Statistics analysis
Data were recorded as (x|-)±S. The results were analyzed by one-factor analysis of variance (ANOVA) with SPSS13.0 statistical software.The results were analyzed by LSD-t if they have homogeneity of variance,by Dunnett-t if they have not.Significance was set at P<0.05.
Results
1. Cells in two groups showed cell shrinkage,floating mucleus concentration,nuclear fragmentation and typical apoptotic bodies.
2. The apoptotic ratio of cultured AM endometrial cells without GnRHa was lower than that in control group and the apoptotic ratio increased with the prolongation of time in two guoups(P<0.01).
3. After GnRHa addition,each group showed higher apoptotic ratio and a trend towards higher apoptotic ratio linked to advanced concentration.Furthermor, apoptotic ratio in study group was significantly higher than in control group at the same time point and same concentration(P<0.01).
Conclusions
1. The abnormality of apoptotic ratio of AM endometrial cells may be associated with the of the AM pathogenesis.
2. GnRHa may increase the apoptotic ratio of cultured AM endometrial cell by autocrine or paracrine,and provides the experimental and theoretical evidence for GnRHa clinical application.
1.研究促性腺激素释放激素激动剂(gonadotropin releasing hormone analogues, GnRHa)对子宫腺肌病(adenomyosis,AM)在位内膜细胞凋亡的影响。
2.探讨AM在位内膜细胞凋亡异常与AM发病机制的关系,为临床治疗提供新的思路及实验依据。
材料与方法:
1.研究对象
收集2007年10月至2008年7月广州医学院附属广州市第一人民医院妇科住院临床诊断为AM行全子宫切除术的患者32例,术后行病理检查确诊,取其在位内膜为研究组。患者年龄34～50岁,平均44.32岁。
收集同期因卵巢上皮性良性肿瘤行卵巢囊肿剔除术患者共20例,术前患者知情同意情况下行诊刮术留取内膜标本,作为对照组。术后病理证实诊断为正常子宫内膜。患者年龄32～46岁,平均42.30岁。
研究组及对照组患者均月经周期规则,术前三个月内未服用过激素类药物,无其他内分泌、免疫和代谢疾病。
2.实验方法
对研究组及对照组子宫内膜细胞为对照组进行体外培养,免疫组化鉴定细胞类型,确定为子宫内膜细胞后用GnRHa 10-7 mol/L、10-5 mol/L两种药物浓度分别作用24、48、72 h三个时间点后用脱氧核苷酸末端转移酶介导的缺口末端标记技术(TdT-mediated biotinylated dUTP nick end labeling,TUNEL)及流式细胞仪AnnexinV-FITC/PI方法检测各组细胞的凋亡率。
3.统计学分析
本研究结果采用SPSS13.0统计软件处理,组间比较用单因素方差分析,方差齐者用LSD-t法,方差不齐者用Dunnett-t法。以P<0.05为差异有统计学意义。
结果:
1. GnRHa作用前AM在位内膜细胞各时间点凋亡率均明显低于正常子宫内膜细胞(P<0.01)。
2. GnRHa作用后各时间点AM在位内膜细胞及正常子宫内膜细胞凋亡率均随作用时间增长明显增加(P<0.01);AM在位内膜细胞凋亡率增加程度显著高于正常子宫内膜细胞(P<0.01)。
结论:
1.AM在位内膜细胞凋亡率异常可能是AM发病机制之一。
2. GnRHa作用后子宫内膜细胞凋亡率较作用前明显增高,表明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,成为GnRHa局部治疗的实验依据。
3. GnRHa作用后两组子宫内膜细胞的凋亡率高于作用前,且随作用时间、浓度的增加而增加,提示在一定作用时间和剂量范围内,GnRHa与子宫内膜细胞的凋亡率具有时间和剂量依赖性。
Objective
1. To investigate the effects of gonadotropin releasing hormone analogues (GnRHa) on apoptosis of cultured adenomyosis(AM) endometrial cells.
2. To determine the roles of abnormality of apoptosis of AM endometrial cell in the pathogenesis of adenomyosis and provide new approach and experimental evidences for the clinical treatment of adenomyosis.
Materials and methods
1. Samples
Eutopic endometrial cells from 32 women who received hysterectomy for AM(study group) and 20 women who received ovarian cyst surgery for benigh ovarian epithelial tumor(control group) of gynaecology department in our hospital were cultrued in vitro.
2. Methods
Detect the apoptotic ratio by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and flow cytometry(AnnexinV-FITC/PI) before and after using GnRHa.
3. Statistics analysis
Data were recorded as (x|-)±S. The results were analyzed by one-factor analysis of variance (ANOVA) with SPSS13.0 statistical software.The results were analyzed by LSD-t if they have homogeneity of variance,by Dunnett-t if they have not.Significance was set at P<0.05.
Results
1. Cells in two groups showed cell shrinkage,floating mucleus concentration,nuclear fragmentation and typical apoptotic bodies.
2. The apoptotic ratio of cultured AM endometrial cells without GnRHa was lower than that in control group and the apoptotic ratio increased with the prolongation of time in two guoups(P<0.01).
3. After GnRHa addition,each group showed higher apoptotic ratio and a trend towards higher apoptotic ratio linked to advanced concentration.Furthermor, apoptotic ratio in study group was significantly higher than in control group at the same time point and same concentration(P<0.01).
Conclusions
1. The abnormality of apoptotic ratio of AM endometrial cells may be associated with the of the AM pathogenesis.
2. GnRHa may increase the apoptotic ratio of cultured AM endometrial cell by autocrine or paracrine,and provides the experimental and theoretical evidence for GnRHa clinical application.
引文
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