GnRH拮抗剂和雌激素联合应用预防顺铂所致卵巢损害的实验研究

Joint Application of Gonadotropin-releasing Hormone Antagonist and Estrogen in Preventing Cisplatin-induced Ovarian Damage in Mouse Model

目的:探讨促性腺激素释放激素拮抗剂(GnRH拮抗剂)和雌激素联合应用对化疗中小鼠卵巢的保护作用。方法:选用40只5～6周龄、体重(18±3)g、性成熟的无特殊病原体(SPF)级BALB/c雌性小鼠,随机分为空白对照组、顺铂(DDP)组、GnRH拮抗剂(西曲瑞克)+雌激素(补佳乐)组、西曲瑞克+补佳乐+顺铂组,每组10只。用药后观察并比较各组小鼠一般状态、体重、卵巢、子宫湿重和卵巢组织结构的变化,比较各组小鼠各级卵泡数量的变化,放射免疫方法测定各组小鼠血清促卵泡生成素(FSH)、雌二醇(E2)水平。结果:顺铂组小鼠血清FSH和E2浓度分别为(1.78±0.23)IU/L和(37.65±1.77)pg/mL,西曲瑞克+补佳乐+顺铂组分别为(1.22±0.13)IU/L和(50.43±2.70)pg/mL,两组分别比较,差异均有统计学意义(P<0.05);顺铂组小鼠卵巢和子宫湿重分别为(8.87±0.69)mg和(53.80±13.65)mg,西曲瑞克+补佳乐+顺铂组分别为(17.19±0.61)mg和(66.97±8.30)mg,两组分别比较,差异均有统计学意义(P<0.05);顺铂组卵泡总数(471±29.71)个,西曲瑞克+补佳乐+顺铂组为(815±25.95)个,两者比较差异有统计学意义(P<0.05)。结论:GnRH拮抗剂和雌激素联合应用能够降低顺铂多小鼠卵巢功能的损伤,起到保护化疗中小鼠卵巢储备功能。

Objective： To investigate the protection of joint application of gonadotropin-releasing hormone antagonist （GnRH Antagonist） and estrogen in preventing cisplatin -induced ovarian failure in mice model. Methods： Forty eugamic female BALB/c mice with an age range from 5 to 6 weeks and bodyweight of （18±3） g were randomly divided into four groups： the blank control, cisplatin（DDP）, GnRHant（cetrorelix）＋estrogen（progynova）, and cetrorelix ＋ progynova ＋ DDP group, with 10 in each group. The general conditions, such as bodyweight change, ovary and uterus wet weight in the groups, were observed and compared after administration, and the numbers of the follicle and histomorphological features of ovary were compared. Radioimmunoassay was used to analyze the serum level of follicle-stimulating hormone （FSH） and estradiol （E2） among the four groups. Results： The concentrations of serum FSH and E2 were （1.78±0.23） IU/L and （37.65±1.77） pg/mL in the DDP group, and were （1.22±0.13） lUlL and （50.43±2.70） pg/ml in cetrorelix ＋ progynova＋DDP group, respectively. There were significant differences between the two groups （P〈0.05）. The average weights of ovarian and uterus were （8.87±0.69） mg and （53.80±13.65） mg in DDP group respectively, which were significantly lower compared to （17.19±0.61） mg and （66.97±8.30） mg in cetrorelix ＋ progynova＋DDP group （P〈0.05）. The total number of follicle was 471±29.71 in DDP group, which was significantly lower compared to 815±25.95 in cetrorelix ＋ progynova＋DDP group （P〈 0.05）. There was statistical significance in the differences between the two groups. Conclusion： GnRHant in combination with estrogen could reduce the chemotherapy-induced ovarian damage in mice, and protect ovarian reserve of mice during the treatment.