文章摘要
熊露,胡雅君,李金丽,等.促性腺激素释放激素拮抗剂对顺铂化疗中小鼠卵巢的保护作用[J].安徽医药,2021,25(7):1286-1289.
促性腺激素释放激素拮抗剂对顺铂化疗中小鼠卵巢的保护作用
Protective effect of GnRH antagonist on ovaries of cisplatin treated mice
  
DOI:10.3969/j.issn.1009-6469.2021.07.004
中文关键词: 卵巢储备功能  药物相关性副作用和不良反应  西曲瑞克  促性腺素释放激素  GnRH拮抗剂  顺铂  小鼠
英文关键词: Ovarian reserve  Drug-related side effects and adverse reactions  Cetrotide  Gonadotropin-releasing hormone  GnRH antagonist  Cisplatin  Mice
基金项目:湖北省卫计委科研项目( 22090100190004);武汉市临床医学科研项目( WX14C04)
作者单位E-mail
熊露 武汉市第一医院生殖医学科湖北武汉 430022  
胡雅君 武汉市第一医院生殖医学科湖北武汉 430022 282314194@qq.com 
李金丽 武汉市第一医院生殖医学科湖北武汉 430022  
刘莉 武汉市第一医院生殖医学科湖北武汉 430022  
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中文摘要:
      目的探讨促性腺激素释放激素(GnRH)拮抗剂对化疗中小鼠卵巢的保护作用。方法 2018年 10月至 2019年 10月,选取华中科技大学同济医学院动物中心购置的 BALB/c雌性小鼠 30只,随机数字表法分为 A组、 B组和 C组,每组 10只,其中 A组腹腔注射等量生理盐水, B组腹腔注射顺铂, C组腹腔注射顺铂和西曲瑞克,采用 HE染色观察各组卵巢组织,测量各组卵巢湿重,放射免疫法检测血清促卵泡生成素( FSH)、黄体生成素( LH)、雌二醇( E2)、抗苗勒管激素( AMH)和基础抑制数 B(INHB)水平,蛋白质印迹法( Western blot)检测卵巢组织凋亡基因( Bax)及凋亡调控基因( Bcl-2)蛋白表达。结果 B组和 C组卵巢湿重明显低于 A组( P<0.05)其中 C组卵巢湿重为( 15.17±0.88)mg,明显高于 B组( 8.95±0.91)mg(P<0.05); B组和 C组原始卵泡、生长卵泡和成熟卵泡明显低,于 A组( P<0.05)其中 C组原始卵泡、生长卵泡和成熟卵泡分别为( 402.00±45.50)个、(110.03±21.28)个和( 40.03±7.89)分,明显高于 B组( 2302±40.10)个、(67.92±19.22)个和( 21.11±6.92)个( P<0.05);与 A组比较, B组生长卵泡及成熟卵泡明显减少,颗粒细胞排列紊乱,卵母细胞形态畸形,黄体细胞结构模糊,细胞核固缩,而 C组有所改善; B组和 C组 FSH和 LH明显高于 A组( P<0.05)而 E2、AMH和 INHB明显低于 A组( P<0.05),其中 C组 FSH和 LH分别为( 0.96±0.20) IU/L和( 3.56±0.91)IU/L,±0.22)IU/L和( 4.80±0.87)IU/L(P<0.05),而 E2、AMH和 INHB分别为( 18.89±1.14) ng/L、(4.10±0.92)IU/L和( 15.51±2.90)mg/ml,明显高于 B组( 9.89±1.92)ng/L、(2.20±0.54)IU/L和( 12.01±2.20)mg/ml(P<0.05); B组和 C组 Bcl-2蛋白相对表达量明显低于 A组( P<0.05)而 Bax蛋白相对表达量明显高于 A组( P<0.05)其中 C组 Bcl-2蛋白相.0,明显低于B组(1.23,对表达量为( 0.302±0.097),明显低于 B组( 0.133±0.076)(,P<0.05),而 Bax蛋白相对表达量为( 0.682±0.,125),明显低于 B组(0.982±0.117)(P<0.05)。结论 GnRH拮抗剂可降低顺铂对小鼠卵巢的损害,保护小鼠卵巢储备功能。
英文摘要:
      Objective To investigate the protective effects of GnRH antagonist on ovarian tissue in mice after chemotherapy.Meth? ods Thirty female BALB/c mice purchased by the Animal Center of Tongji Medical College of Huazhong University of Science andTechnology were selected and divided into group A, B and C according to random digital table method from October 2018 to October2019, with 10 rats in each group. Group A received intraperitoneal injection of normal saline, group B received intraperitoneal injectionof cisplatin, and group C received intraperitoneal injection of cisplatin and cetrorelix. HE staining was used to observe ovarian tissue ineach group, the wet weight of each group was measured, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH)and estradiol (E2) , anti-mullerian hormone (AMH) and basal inhibitory number B (INHB) were measured by reflex immunoassay, western blot was used to detect the expression of Bax and Bcl-2 protein in ovarian tissue.Results The wet weight of ovaries in group B and group C were significantly lower than that in group A (P< 0.05), the wet weight of ovaries in group C was (15.17±0.88) mg, significantly higher than that in group B (8.95±0.91) mg (P< 0.05); The primitive follicles, growing follicles and mature follicles in group B andgroup C were significantly lower than those in group A (P< 0.05). The scores of primitive follicles, growing follicles and mature folliclesin group C were (402.00± 45.50), (110.03±21.28) and (40.03±7.89), which were significantly higher than those in group B (230.02±40.10), (67.92±19.22), (21.11±6.92) (P< 0.05); Compared with group A, the growth follicles and mature follicles of group B were significantly reduced, the arrangement of granulosa cells was disordered, the morphology of oocytes was abnormal, the structure of luteal cellswas fuzzy, the nucleus was pyknosis, while group C was improved; The FSH and LH in group B and group C were significantly higherthan those in group A (P< 0.05), while E2 was significantly lower than those in group A (P < 0.05). FSH and LH in group C were (0.96±0.20) IU/L and (3.56±0.91) IU/L, significantly lower than those in group B(1.23±0.22)IU/L and(4.80±0.87)IU/L (P< 0.05), while E2,AMH and INHB were (18.89±1.14) ng/L, (4.10±0.92) IU/L and (15.51±2.90) mg/ml, which were significantly higher than those in groupB(9.89±1.92)ng/L, (2.20±0.54)IU/L and (12.01±2.20) mg/ml (P< 0.05); The relative expression of Bcl-2 protein in group B and group C were significantly lower than that in group A (P < 0.05), but the relative expression of Bax protein were significantly higher than that in group A (P < 0.05), the relative expression of Bcl-2 protein in group C was (0.302±0.097), significantly lower than that in group B(0.133±0.076) (P < 0.05), and the relative expression of Bax protein was (0.682±0.125 ), was significantly lower than that in group B(0.982±0.117) (P < 0. 05).Conclusion GnRH antagonist can reduce the damage of cisplatin on the ovary of mice and protect the ovarian reserve function of mice.
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