促性腺激素释放激素拮抗剂预防化疗大鼠卵巢功能损害的实验研究  

The effect of gonadotropin-releasing hormone antagonist in preventing chemeotherapy-induced ovarian damage

作　　者：赵雪静[1] 辛晓燕[1] 黄艳红[1] 李欢[1] 

机构地区：[1]第四军医大学西京医院,陕西西安710032

出　　处：《现代肿瘤医学》2008年第6期896-900,共5页Journal of Modern Oncology

摘　　要：目的:探讨促性腺激素释放激素拮抗剂(GnRH拮抗剂)对化疗中大鼠卵巢的保护作用及作用机制。方法:选用40只3-4月龄雌性SD大鼠,随机分为空白对照组,GnRH拮抗剂(西曲瑞克)组,环膦酰胺(CTX)组,西曲瑞克+CTX组,每组10只。用药后比较4组大鼠卵巢、子宫湿重和组织结构的变化,放射免疫方法测定4组大鼠促卵泡生成素(FSH)、雌二醇(E2)水平;采用免疫组化方法检测各用药组对BCL-2蛋白,半胱天冬酶-3蛋白(caspases-3)在卵巢颗粒细胞中表达的影响。结果:光镜下可见CTX对卵巢组织破坏程度较大,使各期卵泡总数显著减少,血FSH升高,E2下降;西曲瑞克能明显改善CTX对卵巢的破坏,使总卵泡数不减并增加初级卵泡比例,FSH升高、E2下降不显著。BCL-2蛋白在西曲瑞克组、联合用药组强表达,与对照组相比无显著差异;在CTX组中BCL-2蛋白表达阴性或弱阳性,与对照组相比有显著差异性。caspases-3蛋白在CTX组强表达,与对照组相比有显著差异性,caspases-3蛋白在西曲瑞克组、联合用药组中不表达或弱表达,与对照组相比无显著差异。结论:GnRH拮抗剂能够起到保护化疗中卵巢的作用,保护机制可能与增强BCL-2抗凋亡及抑制caspases-3凋亡途径有关。Objective：To investigate the effect and mechanism of GnRH Antagonist in preventing chemotherapy - induced ovarian failure in rats. Methods： Young female SD rats of 3 -4 months were randomly derided into four groups： the control group, CTX group, GnRHant（cetrorelix） group, GnRHant ＋ CTX group,10 rats in each group. The ovary weight and histomorphological features were observed. Radioimmunoassay was used to analyze blood level of follicle - stimulating hormone （FSH） and estradiol （E2） among the four groups. Immunohistochemistry was used to analyze the expression of BCL -2 protein and caspase -3 protein in ovaries. Results： As compared with the control group , CTX treatments produced a significant reduction in the total number of follicle, and the weight of ovary and uterus of CTX group were lower than that of the control group, and FSH levels significantly increased and E2 level significantly decreased. Cetrorelix significantly reduced the number of medium - large follicles and increased the number of small one, the total number of follicles did not decrease , cetrorelix showed markedly effects on improving the ovarian morphological construction of rats compared with CTX, and FSH levels and E2 level were similar to control group. The levels of the Bcl - 2 protein in the two cetrorelix groups and control group were significantly higher than that in the CTX group, but levels of the caspases - 3 were on the contrary. Conclusion： GnRHant could reduce the chemotherapy - induced ovarian damage in rats and the role of its against apoptosis might through regulating the expression of the Bcl - 2 and caspases - 3 in the ovary.

关 键 词：GNRH拮抗剂 环膦酰胺 卵巢功能不全 BCL-2 

分 类 号：R730[医药卫生—肿瘤]