长期雌激素替代治疗对大鼠子宫内膜bcl-2和H-ras基因与蛋白表达的影响

Effects of long-term estrogen replacement treatment on the expression of bcl-2 and H-ras in rat endometrium

目的:探讨长期雌激素替代治疗对子宫内膜bcl 2和H ras基因和蛋白表达的影响。方法:将30只5 月龄雌性SD大鼠随机分成3组:对照组(假手术+注射溶剂,n=10)、去势组(双侧卵巢切除术+注射溶剂,n= 10)和雌激素替代组(双侧卵巢切除术+注射雌二醇,n=10)。第13周处死动物,取其子宫称重,HE染色进行病 理分析,测量子宫内膜厚度。用原位杂交和免疫组织化学的方法检测子宫内膜bcl 2mRNA,H rasmRNA及Bcl和 H ras蛋白的表达。结果:去势组子宫湿重、内膜厚度均低于假手术组(P<0.01)和雌激素替代组(P<0.01)。替 代组出现1例单纯性增生和1例鳞状细胞化生。替代组bcl 2和H rasmRNA和Bcl和H ras蛋白表达量明显高于 去势组(P<0.01),与假手术组差异无统计学意义。结论:长期雌激素替代治疗能抑制子宫内膜萎缩,且会出现单 纯性增生或鳞状细胞化生,具有潜在增加子宫内膜癌的发病风险。雌激素可通过增加bcl 2和H rasmRNA及Bcl 和H ras蛋白的表达,抑制子宫内膜细胞的凋亡,促进细胞增殖。

Objective To investigate the effects of long-term estrogen replacement treatment (ERT) on the expression of bcl-2 and H-ras in rat endometrium. Methods Thirty 5-month-old SD female rats were randomly divided into 3 groups: Control group (sham operated and vehicle injected, n=10), OVX group (OVX operated and vehicle injected, n=10), and ERT group (OVX operated and 17 β-estradiol injected, n=10). The rats were killed in the 13th week and the uteri were isolated and weighed, pathologically analyzed, and we measured the thickness of the endometrium. Immunochemistry and in situ hybridization analysis were used to examine the changes of bcl-2 and H-ras mRNA and Bcl and H-ras protein expression in the endometrium of the rats. Results Uterine weight and endometrial thickness of OVX decreased much more than those of the control (P<0.01) and ERT rats (P<0.01). One simple hyperplasia and one squamous metaplasia of endometrium were found in ERT rats. Quantitatively, bcl-2 and H-ras mRNA and Bcl and H-ras protein level of ERT were higher than those of OVX rats (P<0.01), and there were no statistical significances between the ERT group and the control rats. Conclusion Long-term estrogen replacement can keep the endometrium from atrophy, and lead to the genesis of simple hyperplasia and squamous metaplasia of the endometriun, which can increase the risk of endometrial carcinomas. Estrogen may inhibit apoptosis and promote the proliferation of endometrial cells through increasing the expression of bcl-2 and H-ras mRNA and Bcl-H-ras proteins.