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不同浓度顺铂对C57BL/6小鼠卵巢功能的影响

Effects of different concentrations of cisplatin on ovarian function in C57BL/6 mice

  • 摘要:
    目的 通过研究不同浓度顺铂对C57BL/6小鼠卵巢功能的影响,探讨能够引起C57BL/6小鼠卵巢早衰的最低有效浓度,从而为临床研究提供一种安全、可靠、便捷的早发性卵巢功能不全(POI)模型构建方案。
    方法 随机选择SPF级雌性C57BL/6小鼠(6~8周)60只,随机分为对照组、剂量1.0组(1 mg/kg)、剂量1.5组(1.5 mg/kg)、剂量2.0组(2 mg/kg),给药组均连续腹腔注射7 d顺铂。
    结果 1.0组小鼠卵巢受损较轻,卵巢组织形态、卵泡计数及血清激素水平与对照组相比,变化程度较小,无法用于建模;1.5组小鼠卵巢受损较重,体质量下降平稳,一般状态好,死亡率低,动情周期恢复率低,卵巢组织形态、卵泡计数及血清激素水平与对照组差异均有统计学意义(P < 0.05),但变化较为平缓,适宜建立POI模型;2.0组小鼠卵巢受损严重,体质量下降明显,全身状况差,出现持续的动情间期,卵巢组织形态、卵泡计数及血清激素水平与对照组差异均有统计学意义(P < 0.05),但变化大,不利于实验研究。
    结论 1.5 mg/kg为建立C57BL/6小鼠POI模型的合适有效浓度,采用该给药方案建立的模型,卵巢组织损伤较为稳定,能够较好地模拟POI患者的激素水平变化,动物耐受性好,有利于治疗研究的开展,适用于POI治疗方案的评价。

     

    Abstract:
    Objective To study the effect of cisplatin of different concentrations on the ovarian function in C57BL/6 mice, and to explore the minimum effective concentration that can cause premature ovarian insufficiency (POI) in C57BL/6 mice, aiming to provide a safe, reliable, and convenient POI model for clinical research.
    Methods Totally, 60 female C57BL/6 mice (6-8 weeks) of SPF grade were randomly divided into control group, dose 1.0 group (1 mg/kg), dose 1.5 group (1.5 mg/kg), and dose 2.0 group (2 mg/kg), different concentrations of cisplatin were administered by the traditional intraperitoneal route for 7 days in cisplatin group.
    Results In 1.0 group, ovarian tissue morphology, follicle count, and serum hormone levels were slightly different from those in the control group, but without statistical significance, therefore could not be used for modeling. In 1.5 group, the ovaries of mice were damaged heavily, their weight dropped steadily, but the general state was good, the mortality rate was low, the recovery rate of estrous cycle was low, and the ovarian histomorphology, follicle count, and serum hormone levels had statistical significance changes compared with those in the control group, but the degree of change was relatively gentle, which was suitable for the establishment of POI model. In 2.0 group, the ovaries of mice were severely damaged, their body weight dropped dramatically, the general condition was poor, and there were persistent estrous intervals. The ovarian histomorphology, follicle count, and serum hormone levels were significantly different from those in the control group, but the changes were dramatic, which was not conducive to the experimental study.
    Conclusions The suitable and effective concentration of cisplatin for establishing POI model in C57BL/6 mice is 1.5 mg/kg. The ovarian tissue damage of the model established by this drug regimen is relatively stable, which can well simulate the changes in hormone levels of POI patients, and the animal has a good tolerance, which is conducive to the development of treatment studies and more suitable for the evaluation of POI treatment regimen.

     

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