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目的:探讨化疗时抗苗勒氏管激素(anti-Müllerian hormone,AMH)作为预测大鼠卵巢储备功能状态的可行性。方法:雌性SD大鼠24只,随机分为3组:对照组(NS)、顺铂化疗低剂量组(4.5 mg/kg,CL)和高剂量组(6.0 mg/kg,CH),每组8只。免疫组织化学染色检测AMH在卵巢的表达,光学显微镜下计数AMH阳性卵泡百分比,ELISA检测血清AMH、FSH水平。结果:各组大鼠卵巢组织均可见AMH表达,主要位于初级卵泡、窦前卵泡及小窦状卵泡的颗粒细胞,给予顺铂12 d后,AMH的表达强度减弱、范围缩小。CL组和CH组的AMH阳性卵泡百分比均较NS组明显降低(P<0.05)。卵巢AMH强阳性的卵泡百分比随顺铂剂量的增高而降低(P<0.05),CH组最低,而AMH阴性或弱阳性卵泡百分比升高;血清AMH水平变化与免疫染色结果相平行,即顺铂CL组及CH组的AMH水平较对照组明显降低,且呈剂量依赖性(P<0.01)。血清FSH水平顺铂化疗后虽有增高趋势,但各组间未见明显差异。结论:临床常用化疗药顺铂可损伤正常卵巢组织,使颗粒细胞表达AMH减少,致使卵巢储备功能下降,血清AMH水平能够较好地反映这一变化,作为预测化疗后卵巢储备功能状态的指标具有较高的可信性。
Objective: To investigate the feasibility of using anti-Müllerian hormone (AMH) as a predictor of ovarian reserve status during chemotherapy. Methods: Twenty-four female SD rats were randomly divided into three groups: control group (NS), cisplatin low-dose chemotherapy group (4.5 mg / kg, CL) and high dose group (6.0 mg / kg, 8 only The expression of AMH in ovary was detected by immunohistochemical staining. The percentage of AMH positive follicles was counted under light microscope. The levels of serum AMH and FSH were detected by ELISA. Results: The expression of AMH was observed in all groups of ovarian tissues, mainly in the granulosa cells of primary follicles, preantral follicles and small sinusoid follicles. After cisplatin administration for 12 days, the expression intensity of AMH was weakened and the range was narrowed. The percentage of AMH positive follicles in CL group and CH group was significantly lower than that in NS group (P <0.05). Ovarian AMH strong positive follicles decreased with the increase of cisplatin dose (P <0.05), CH group the lowest, while the percentage of AMH negative or weakly positive follicles increased; serum AMH levels and immunostaining results parallel to cisplatin AMH levels in CL and CH groups were significantly lower than those in control group (P <0.01). Serum FSH levels despite cisplatin chemotherapy increased trend, but no significant differences between the groups. Conclusion: Cisplatin, a commonly used chemotherapeutic drug, can damage normal ovarian tissue and decrease AMH expression in granulosa cells, resulting in decreased ovarian reserve and serum AMH level, which can be used as an index to predict ovarian reserve functional status after chemotherapy Higher credibility.