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

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。

Experimental study on protective effects of enantone and vitamin E on cisplatin-induced ovary damage in rats

Objective:To observe the protective effects of enantone and vitamin E on cisplatin-induced ovary damage in rats.Methods:64 12-week-old SD female rats were divided into four groups randomly.The rats in group A were injected normal saline(2 ml/d) intraperitoneally,the rats in group B were injected cisplatin(2 mg/(kg·d)) intraperitoneally,the rats in group C were injected cisplatin(2 mg/(kg·d)) intraperitoneally and enantone(0.25 mg) subcutaneously,the rats in group D were injected cisplatin(2 mg/(kg·d)) intraperitoneally and administered vitamin E(50 mg/(kg·d)) through a gastric tube,all the rats were treated for ten days.Body weight,weights of ovary and uterus were detected at the end of administration and on the 30th day after administration;the amount of follicles and their diameters,pathological changes of ovary and uterus were observed under light microscope;the levels of estrogen and follicule-stimulating hormone were detected.Results:Compared with group A,the rats in group B,C,D appeared dispirited and poor appetite,with low body weight and uterus weight(P<0.05) at the end of administration,especially group B;on the 30th day after administration,the above-mentioned indexes improved(P<0.05),but the body weights of group B,C,D were lighter than that of group A;the body weights of group C,D were heavier than that of group B(P<0.05).The mucous membrane of uterus in group B,C,D became thinner,apocrine secretion occurred;on the 30th day after administration,the thickness of endometrium and secretory volume of glands improved.At the end of administration,the amounts of growing follicles and mature follicles decreased dramatically,regression phenomenon occurred(P<0.05).The amounts of mature follicles in groupB,C,D were lower than that in group D(P<0.05).The amount of mature follicles in group C was higher than those in group A,B,D(P<0.05).On the 30th day after administration,the amount of mature follicles in group B was lower than those in the other groups(P<0.05),while the amount of mature follicles in group C was higher than those in the other groups,the amount of primordial follicles in group C was lower than those in the other groups(P<0.05).At the end of administration,the levels of follicule-stimulating hormone in group B,C,D increased,while the levels of estrogen reversed(P<0.05),especially group B(P<0.05).On the 30th day after administration,the levels of follicule-stimulating hormone in group C,D decreased,while the levels of estrogen reversed(P<0.05).Conclusion:Cispatin has obvious toxicity to overy in rats.Enantone may increase the amount of primordial follicles and keep the follicles from growing.Vitamin E may protect growth follicles and mature follicles in rats.