Objective: To compare the impact on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model. Methods: Thirty 8-weeks old female Sprague Dawley rats were randomly assigned to control group (group A, n=10), intraperitoneal chemotherapy group (group B, n=10) and intravenous chemotherapy group (group C, n=10). Cisplatin was diluted by normal saline (NS) into 4 mg/ml. On the first day of chemotherapy, 0.2 ml cisplatin dilution was injected into the abdomen of rats in group B, isodose cisplatin was injected into vein and 1.8 ml NS was injected into abdomen of rats in group C, 2.0 ml NS was injected into abdomen of rats in group A for control. Feed the three groups rats and test the anti-Mullerian hormone (AMH) in serum on day 0 (just before injection), day 10 and day 20 by ELISA, count the numble of follicle in bilateral ovaries on day 20. Results: (1) The levels of serum AMH in the three groups before and after chemotherapy were compared: ① comparison between groups: On day 10 and day 20, the AMH level in group B [(64.5±2.9), (68.6±3.4) ng/L] and group C [(76.1±4.9), (91.3±3.9) ng/L] was significantly lower than that in group A [(120.1±5.3), (121.7±4.6) ng/L; P<0.01], AMH level in group B was significantly also lower than that in group C (P=0.000). ② Comparison within groups: the AMH level on day 0 was significantly lower than that on day 10 and day 20 in group A (P<0.01), but there was no significant difference between day 10 and day 20 (P=0.427). The AMH level on day 0 was significantly higher than those on day 10 and day 20 in group B (P<0.01) and group C (P<0.01). There was no difference in AMH level between day 10 and day 20 (P=0.124) in group B, but the level was significant lower on day 10 than that on day 20 in group C (P=0.011). (2)Comparison of the number of follicles in ovaries of three groups 20 days after chemotherapy: the follicles number in group A (35±13) was greater than that in group B (16±9, P=0.003) and similar with group C (31±16, P=0.474) on day 20. The follicles number in group B was significantly less than that in group C (P=0.018). Conclusions: In the present study, both intravenous and intraperitoneal chemotherapy have impacts on ovarian reserve function and the latter might be more serious. The level of AMH will rise again over time after chemotherapy and rats undergo intravenous chemotherapy would recover faster. The results suggest that the ovarian reserve function need more time to recover after intraperitoneal chemotherapy. For patients with ovarian cancer who want to preserve fertility function, intravenous chemotherapy might be more appropriate.
目的： 通过对比顺铂腹腔化疗与静脉化疗前后大鼠血清抗苗勒管激素（AMH）水平及其卵巢内卵泡数量的变化，探讨不同化疗途径对卵巢储备功能的影响。 方法： 取8周龄的成熟雌性SD大鼠30只，采用随机数字表法编号后将大鼠随机分为3组，每组10只。腹腔化疗组：大鼠腹腔内注入0.2 ml顺铂稀释液（4 mg/ml）+1.8 ml生理盐水；静脉化疗组：大鼠尾静脉注入0.2 ml顺铂稀释液，腹腔内注入1.8 ml生理盐水；空白对照组：大鼠腹腔内注入2.0 ml生理盐水。采用ELISA法分别于化疗前[即化疗当日注射顺铂前（d(0)）]以及化疗后第10、20天（d(10)、d(20)）检测大鼠血清AMH水平；并于d(20)取大鼠双侧卵巢制作病理切片，显微镜下观察其最大切面的各级卵泡并计数。 结果： （1）3组大鼠化疗前后不同时间血清AMH水平的比较：①组间比较：化疗后d(10)、d(20)，腹腔化疗组[分别为（64.5±2.9）、（68.6±3.4）ng/L]、静脉化疗组[分别为（76.1±4.9）、（91.3±3.9）ng/L]大鼠血清AMH水平均低于空白对照组[分别为（120.1±5.3）、（121.7±4.6）ng/L]，分别比较，差异均有统计学意义（P<0.01）；且腹腔化疗组均低于静脉化疗组，分别比较，差异也均有统计学意义（P<0.01）。②组内比较：腹腔化疗组、静脉化疗组化疗前（即d(0)）大鼠血清AMH水平[分别为（101.4±3.8）、（101.7±4.0）ng/L]，均高于各自的d(10)、d(20)，分别比较，差异均有统计学意义（P<0.01）；且静脉化疗组d(10)低于d(20)，两者比较，差异也有统计学意义（P=0.011）；但腹腔化疗组d(10)与d(20)比较，差异则无统计学意义（P=0.124）。空白对照组大鼠血清AMH水平，d(0)[（98.7±2.7）ng/L]低于d(10)、d(20)，分别比较，差异均有统计学意义（P<0.01）；而d(10)与d(20)相比，差异则无统计学意义（P=0.427）。（2）3组大鼠化疗后d(20)卵巢内卵泡数的比较：化疗后d(20)，腹腔化疗组大鼠的卵泡数[（16±9）个]少于静脉化疗组、空白对照组[分别为（31±16）、（35±13）个]，分别比较，差异均有统计学意义（P=0.018，P=0.003）；而静脉化疗组大鼠的卵泡数略少于空白对照组，两组比较，差异无统计学意义（P=0.474）。 结论： 治疗浓度的顺铂经腹腔及静脉途径给药后大鼠血清AMH水平均明显下降，且经腹腔途径给药后大鼠血清AMH水平下降更明显、恢复排卵功能需要的时间更长。因此，选择静脉化疗可能较有利于卵巢储备功能的保护。.
Keywords: Cisplatin; Fertility preservation; Injections, intraperitoneal; Injections, intravenous; Ovarian neoplasms.