抑那通和维生素E对顺铂所致大鼠卵巢功能损伤保护的实验研究

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目的:通过使用抑那通(亮丙瑞林)、维生素E,观察其对顺铂所致大鼠卵巢功能损伤的保护作用。方法:选择SPF级别12周龄SD雌鼠64只,随机分4组。A组为正常对照,腹腔注射生理盐水,2 m l/d。B组为顺铂组,C组为抑那通+顺铂组,D组为维生素E+顺铂组。C组皮下注射抑那通0.25 mg/只。B、C、D组腹腔注射顺铂,2mg/(kg.d),D组灌胃维生素E 50 mg/(kg.d),连续用药10天。给药结束后及结束后30天分别每组处死8只,称体重、卵巢及子宫重量,光镜观察卵泡数量及卵泡直径和各级卵泡的计数,卵巢和子宫病理学观察;经心脏采血测雌二醇(E2)、卵泡刺激素(FSH)。结果:给药结束后B、C、D组和A组相比,大鼠精神及饮食状况差,体重及子宫重量下降(P<0.05),B组最明显(P<0.05);给药后30天大鼠精神状态有改善,4组体重增加(P<0.05),但B、C、D组仍比A组轻;C、D组比B组体重增加明显(P<0.05)。给药结束后B、C、D组子宫黏膜层变薄,胞质分泌泡少,纤维成分多,子宫腺体少,有顶浆分泌现象;给药后30天,B、C、D组子宫内膜厚度及腺体量有所改善。给药结束后B组生长卵泡、成熟卵泡数明显减少,间质有纤维化和坏死,粒细胞层明显减少,呈退行性变化(P<0.05)。B、C、D组的成熟卵泡数少于A组(P<0.05)。C组与其余3组相比原始卵泡数增多(P<0.05)。给药后30天,B组成熟卵泡数减少(P<0.05),C组原始卵泡数减少,成熟卵泡数明显增多(P<0.05)。给药结束后B、C、D组FSH升高,E2下降(P<0.05),且B组与C、D组相比,FSH升高,E2下降更明显(P<0.05);给药后30天,C、D组FSH降低,E2升高(P<0.05)。结论:顺铂对大鼠机体及卵巢有毒性作用;抑那通可使原始卵泡数增多,使卵泡处于静止期;维生素E对大鼠的生长卵泡和成熟卵泡有保护作用。 Objective: To observe the protective effects of cisplatin on ovarian dysfunction induced by cisplatin in rats by using pentamidine (Leuprorelin) and vitamin E (E). Methods: Sixty female Sprague-Dawley (SD) females aged 12 weeks old were randomly divided into four groups. Group A was normal control, intraperitoneal injection of saline, 2 m l / d. B group was cisplatin group, C group was the combination of nifedipine + cisplatin group, D group was vitamin E + cisplatin group. Group C subcutaneous injection of nadropamide 0.25 mg / only. Groups C, D were intraperitoneally injected with cisplatin (2 mg / (kg · d)). Group D was given 50 mg / (kg · d) vitamin E for 10 days. After the treatment and after 30 days, each group was sacrificed 8, weighing, ovarian and uterine weight, the number of follicles observed by light microscopy and follicular diameter and follicle count, ovarian and uterine pathological observation; Estradiol (E2), follicle stimulating hormone (FSH). Results: Compared with group A, the rats in group B, C and D had worse mental status and diet, weight and uterus weight decreased (P <0.05) The mental status of the rats in the 30th day was improved, and the weight of the rats in 4 groups was increased (P <0.05). However, the rats in groups B, C and D were still lighter than those in group A; the weights of rats in groups C and D increased significantly (P <0.05). After the administration, the uterine mucosa of group B, C, D became thinner, the secretion of cytoplasm was less, the fiber content was more, the number of uterine glands was less, Intimal thickness and gland volume improved. At the end of the administration, follicles grew in group B, the number of mature follicles was significantly reduced, interstitial fibrosis and necrosis, granular cell layer was significantly reduced, showed a degenerative change (P <0.05). The number of mature follicles in groups B, C and D was less than that in group A (P <0.05). Compared with the other three groups, the number of primordial follicles increased in group C (P <0.05). At 30 days after administration, the number of mature follicles in group B decreased (P <0.05), the number of primordial follicles in group C decreased and the number of mature follicles increased significantly (P <0.05). FSH increased and E2 decreased (P <0.05) in group B, C and D at the end of the treatment, FSH increased and E2 decreased more significantly than group C and D (P <0.05) On the 30th day, the FSH in group C and D decreased and E2 increased (P <0.05). CONCLUSION: Cisplatin has toxic effect on the body and ovary of rats. Epirubicin can increase the number of primordial follicles and keep the follicles in a quiescent state. Vitamin E has a protective effect on the growing follicles and mature follicles in rats.
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