化疗损伤性卵巢功能早衰小鼠动物模型的研究

Study of Mouse Model with Premature Ovarian Failure Induced by Chemotherapeutic Lesions

目的探索建立化疗损伤性卵巢功能早衰动物模型的适宜方法及最佳时间。方法以70只ICR雌性小鼠为研究对象，腹腔连续注射顺铂7—14d，观察不同剂量和时间条件下顺铂对小鼠的体重、卵巢功能、肝肾毒性及卵巢组织抗氧化系统各指标的变化。结果顺铂可引起小鼠体重明显下降，卵巢功能减退，出现肝肾毒性，并可引起卵巢抗氧化及氧化损伤指标的异常，与对照组比较均有明显差异。结论3．0-4．0mg／（kg·bw）的顺铂作用7d后即可引起小鼠出现明显的卵巢功能衰退、肝肾损伤，氧化损伤是顺铂产生其毒性作用的可能机制之一。该模型的生殖内分泌和病理组织学变化，与人类化疗损伤性卵巢功能早衰病变过程相似。

Objective To investigate an applicable method and optimal time in establishment of the animal model for chemotherapy-induced premature ovarian failure. Methods 70 female ICR mice were injected i. p. with cis-diamine dichloroplatinum （CDDP） everyday for 7 - 14 days at different doses. The effects of adminstration of CDDP at different doses and different time on weight, ovarian function, hepatoxicity, nephrotoxicity and indexes of ovarian antioxidant system were observed. Results CDDP induced body weight decrease, ovarian hypofunction, obvious hepatoxocity and nephrotoxity, abnormality of ovarian antioxidant function and oxidative damage. The changes showed significant difference from those of control group （ P 〈 0.05）. Conclusion 3.0 - 4.0 mg/（kg·bw） dose of cisplatin can lead to obvious damage to the function of ovary, liver and kidney in a 7-day treatment. Oxidative damage is one of the possible mechanism of cisplatin toxicity. The pathological changes of reproductive system in this model are similar with that of chemotherapy-induced premature ovarian failure in human.