Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatin-induced toxicity: a controlled experimental animal study.
Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatin-induced toxicity: a controlled experimental animal study.
复制标题
DOI：
10.1186/1477-7827-11-16
复制
发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Li X;Kang X;Deng Q;Cai J;Wang Z
随着手术和化疗治疗的不断改进，越来越多的肿瘤患者获得长期生存，甚至可以完全治愈。然而，广泛用于治疗各种类型癌症的含铂药物会导致月经失调和卵巢衰竭，进而导致不孕。迄今为止，促性腺激素释放激素（GnRH）激动剂（GnRHa）和拮抗剂（GnRHant）被报道通过抑制雌性性腺轴而在化疗中起卵巢保护剂的作用。然而，它们都有限制其使用的缺点。GnRHa在给药后的第一周内引起发作效应，并且没有长效GnRHant药物可用。GnRHa联合GnRHant可防止GnRHa的发作效应，并迅速抑制雌性性腺轴。一些小样本量的临床研究报告了有争议的结论。在这项严格对照的动物研究中，我们研究了GnRHa和GnRHant联合治疗的优势。将12周龄大鼠分为六组：对照组、顺铂（CDDP）组、GnRHa组、GnRHant组、GnRHa和GnRHant联合组（sht，短期）组以及GnRHa和GnRHant联合组（lng，长期）组。长期组给予曲普瑞林（1 mg/kg·d，连用14 d）、西曲瑞克（0.5mg/kg·d，连用10 d）、曲普瑞林（1 mg/kg·d，连用10 d）+西曲瑞克（0.5mg/kg·d，连用10 d），短期组给予曲普瑞林（1 mg/kg·d，连用3d）。对照组和顺铂组给予生理盐水1 ml/kg·d，连续10 d。然后，除对照组外，各组均接受顺铂（1 mg/kg·d，持续10天），对照组如上所述再接受生理盐水10天。采集血样检测血清E2、LH、FSH水平。给药后还观察了发情周期。最后，收集双侧卵巢进行组织学研究和卵泡计数。我们在GnRHa治疗的大鼠中观察到了发作效应，但在任何联合治疗组中均未观察到。GnRHa、GnRHant、联合用药组和联合用药组的正常周期百分比分别从CDDP组的0%增加到25.0%、33.3%、66.7%和41.7%。GnRHa、GnRHant和联合用药（GnRHa + GnRHant + GnRHa GnRH激动剂与拮抗剂的组合完全防止了顺铂诱导的大鼠性腺毒性的发作效应，并增强了卵巢的保护作用。
With the continuous improvement of surgery and chemotherapeutic treatments, many tumour patients increasingly achieve long-term survival and can even be completely cured. However, platinum-containing drugs, which are widely used to treat a variety of types of cancer, cause menstrual disorders and ovarian failure, which in turn lead to infertility. Thus far, gonadotropin releasing hormone (GnRH) agonist (GnRHa) and antagonist (GnRHant) are reported to act as protective agents of the ovary in chemotherapy through the inhibition of the female gonadal axis. Nevertheless, they both have disadvantages that limit their use. GnRHa causes a flare-up effect during the first week after administration, and no long-acting GnRHant agent is available. GnRHa combined with GnRHant may prevent the flare-up effect of GnRHa and rapidly inhibit the female gonadal axis. Several clinical studies with small sample sizes have reported controversial conclusions. In this strictly controlled animal study, we investigated the advantages of combination treatment with GnRHa and GnRHant. Rats aged 12 weeks were divided into six groups: Control, cisplatin (CDDP), GnRHa, GnRHant, Combination (sht, short-term) and Combination (lng, long-term) of GnRHa and GnRHant. The last four groups received Triptorelin (1 mg/kg·d, for 14 days), Cetrorelix (0.5 mg/kg·d, for 10 days), a combination of Triptorelin (1 mg/kg·d, for 10 days) and Cetrorelix (0.5 mg/kg·d, for 10 days) in the long-term group and for 3 days in the short-term group. The Control and CDDP groups received saline (1 ml/kg·d, for 10 day). Then, all groups apart from the Control group received cisplatin (1 mg/kg·d, for 10 days), and the Control group received another 10 days of saline as described above. Blood samples were collected to detect the serum levels of E2, LH and FSH. Observation of oestrous cyclicity was also performed after drug administration. Finally, bilateral ovaries were collected for histological study and follicle counting. We observed a flare-up effect in rats treated with GnRHa, but not in any of the combination groups. The percentage of normal cyclicity increased from 0% in the CDDP group to 25.0%, 33.3%, 66.7% and 41.7%, in the GnRHa, GnRHant, combination (lng) and combination (sht) groups, respectively. Pretreatment with GnRHa, GnRHant and combination (lng) significantly protected the primordial follicles from destruction by preserving 57.6%, 63.4%, 87.1% and 60.4% of the follicles, respectively. The combination of a GnRH agonist with antagonist completely prevented the flare-up effect and enhanced the protective effect of the ovary from cisplatin-induced gonadotoxicity in rats.
登录
查看更多内容
影响因子：
64.8
作者：
Johnson, J;Canning, J;Tilly, JL
通讯作者：
Tilly, JL
影响因子：
5.8
作者：
Blumenfeld, Zeev
通讯作者：
Blumenfeld, Zeev
影响因子：
3.6
作者：
Parborell, F;Irusta, G;Tesone, M
通讯作者：
Tesone, M
DOI：
10.1016/j.ejogrb.2009.12.028
发表时间：
2010-04-01
影响因子：
2.6
作者：
Tan, Shun-Jen;Yeh, Yu-Chi;Chen, Chi-Huang
通讯作者：
Chen, Chi-Huang
DOI：
10.1111/j.1479-828x.2011.01346.x
发表时间：
2011-10-01
影响因子：
1.7
作者：
Whitehead, Julie;Toledo, Manuela G.;Stern, Catharyn J.
通讯作者：
Stern, Catharyn J.