促性腺激素释放激素拮抗剂对盆腔放疗所致卵巢功能损伤的防护作用

目的 研究促性腺激素释放激素拮抗剂（GnRH-ant）对盆腔放疗所致大鼠卵巢功能损伤的防护作用及潜在保护机制。方法 1.雌性Wistar大鼠10只，采用随机数字表法分为促性腺激素释放激素激动剂（GnRH-a）组与GnRH-ant组，分别皮下注射醋酸戈舍瑞林0.25 mg（1次）、醋酸西曲瑞克5 μg（每天，连续10 d），动态观察两组大鼠血清黄体生成素（LH）和雌二醇（E2）水平的变化。2.雌性Wistar大鼠40只，采用随机数字表法分为对照组、GnRH-ant组、放疗组、GnRH-ant+放疗组，分别给药及盆腔60Co照射200 cGy后，检测卵巢湿重与血清卵泡刺激素（FSH）、E2和抗缪勒管激素（AMH）的水平；分类计数卵巢内各级卵泡总数，评价卵巢功能的保护情况。两组间比较采用独立样本t检验，多组间比较采用最小显著性差异法。结果 1.GnRH-a组的LH、E2水平短暂升高后逐渐下降，10 d左右达最低值；GnRH-ant组的LH、E2水平迅速下降，4 d左右达最低值，且无“点火效应”。2.与放疗组比较，GnRH-ant+放疗组的卵巢湿重更高（37.8±7.1）mg vs.（58.3±9.1）mg，t=5.61，P=0.000]、E2水平较高（16.64±6.54）pg/mL vs.（57.49±13.45）pg/mL，t=8.64，P=0.000]、FSH水平较低（27.74±7.75）mIU/mL vs.（8.35±1.43）mIU/mL，t=7.75，P=0.000]、AMH水平较高（2.23±0.72）mIU/mL vs.（5.47±1.32）mIU/mL，t=6.81，P=0.000]、原始及初级卵泡数明显更高（27.6±5.1 vs.46.2±12.3，t=4.42，P=0.000），且差异均有统计学意义。结论 GnRH-ant能迅速有效地抑制大鼠卵巢功能的损伤，且无给药后“点火效应”。放疗前给予GnRH-ant，会将大鼠卵巢内的卵泡发育停滞于原始及初级卵泡阶段，减轻放疗辐射对卵巢功能的损伤。

Protective effect of gonadotropin releasing hormone antagonist on ovarian function injury induced by pelvic radiotherapy

Objectives To investigate the protective effect and mechanism of a gonadotropin-releasing hormone antagonist (GnRH-ant) against an ovarian function injury induced by pelvic radiotherapy in a rat model.Method 1. Ten female Wistar rats were randomly assigned to gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-ant groups using the random number table method. The rats were subcutaneously injected with goserelin (0.25 mg once) or cetrorelix (5 μg/day for 10 days). Changes in luteinizing hormone (LH) and estradiol (E2) in each group were dynamically observed. 2. Forty female Wistar rats were randomly divided into four groups (control, GnRH-ant, R, and GnRH-ant+R) and then given corresponding treatments. Ovarian wet weight, levels of serum LH, E2, and AMH, and the number of follicles at every stage were compared between groups through analysis of variance and independent sample t-test.Results1. In the GnRH-a group, LH and E2 levels increased initially and then gradually decreased, reaching a low value in approximately 10 d. In the GnRH-ant group, LH and E2 levels decreased rapidly, reaching the minimum value in 4 d without flare-up effect. 2. After pelvic radiotherapy, the ovarian wet weight in the GnRH-ant+R group was significantly higher(58.3±9.1) mg vs. (37.8±7.1) mg, t=5.61, P=0.000] than that in group R. In the GnRH-ant+R group, the levels of E2(57.49±13.45) pg/mL vs. (16.64±6.54) pg/mL, t=8.64, P=0.000] and AMH(5.47±1.32) mIU/mL vs. (2.23±0.72) mIU/mL, t=6.81, P=0.000] were significantly higher than those in group R. The FSH level in GnRH-ant+R group was significantly lower(27.74±7.75) mIU/mL vs. (8.35±1.43) mIU/mL, t=7.75, P=0.000] than that in group R. The number of primordial and primary follicles in group GnRH-ant+R was significantly higher (46.2±12.3 vs. 27.6±5.1, t=4.42, P=0.000) than that in group R.Conclusions GnRH-ant can rapidly induce ovarian inhibition without flare-up effect. Subcutaneous injection of GnRH-ant before pelvic radiotherapy can inhibit the ovary and stop the follicles in the primary and primordial follicle stages, thus reducing the damage induced by radiotherapy.