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[大鼠模型中顺铂腹腔或静脉化疗后卵巢储备功能的实验对照研究]

[An experiment control study on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model].

作者信息

Fan B Z, Xia H, Chu L, Tong X W

机构信息

Department of Obstetrics and Gynecology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2017 Apr 25;52(4):249-253. doi: 10.3760/cma.j.issn.0529-567X.2017.04.007.

Abstract

To compare the impact on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model. Thirty 8-weeks old female Sprague Dawley rats were randomly assigned to control group (group A, 10), intraperitoneal chemotherapy group (group B, 10) and intravenous chemotherapy group (group C, 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. (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; 0.01], AMH level in group B was significantly also lower than that in group C (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 (0.01), but there was no significant difference between day 10 and day 20 (0.427). The AMH level on day 0 was significantly higher than those on day 10 and day 20 in group B (0.01) and group C (0.01). There was no difference in AMH level between day 10 and day 20 (0.124) in group B, but the level was significant lower on day 10 than that on day 20 in group C (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, 0.003) and similar with group C (31±16, 0.474) on day 20. The follicles number in group B was significantly less than that in group C (0.018). 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.

摘要

比较顺铂腹腔或静脉化疗对大鼠模型卵巢储备功能的影响。将30只8周龄雌性Sprague Dawley大鼠随机分为对照组(A组,10只)、腹腔化疗组(B组,10只)和静脉化疗组(C组,10只)。顺铂用生理盐水(NS)稀释成4mg/ml。化疗第一天,向B组大鼠腹腔注射0.2ml顺铂稀释液,向C组大鼠静脉注射等剂量顺铂并向腹腔注射1.8ml NS,向A组大鼠腹腔注射2.0ml NS作为对照。饲养三组大鼠,在第0天(注射前)、第10天和第20天通过ELISA检测血清抗苗勒管激素(AMH),在第20天计数双侧卵巢卵泡数量。(1)比较三组化疗前后血清AMH水平:①组间比较:在第10天和第20天,B组[(64.5±2.9),(68.6±3.4)ng/L]和C组[(76.1±4.9),(91.3±3.9)ng/L]的AMH水平显著低于A组[(120.1±5.3),(121.7±4.6)ng/L;P<0.01],B组的AMH水平也显著低于C组(P<0.000)。②组内比较:A组第0天的AMH水平显著低于第10天和第20天(P<0.01),但第10天和第20天之间无显著差异(P=0.427)。B组和C组第0天的AMH水平显著高于第10天和第20天(P<0.01)。B组第10天和第20天的AMH水平无差异(P=0.124),但C组第10天的水平显著低于第20天(P=0.011)。(2)化疗20天后三组卵巢卵泡数量比较:第20天A组卵泡数量(35±13)多于B组(16±9,P=0.003),与C组(31±16,P=0.474)相似。B组卵泡数量显著少于C组(P=0.018)。在本研究中,静脉和腹腔化疗均对卵巢储备功能有影响,且后者可能更严重。化疗后随着时间推移AMH水平会再次升高,接受静脉化疗的大鼠恢复更快。结果表明腹腔化疗后卵巢储备功能需要更长时间恢复。对于希望保留生育功能的卵巢癌患者,静脉化疗可能更合适。

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