环磷酰胺致大鼠卵巢功能不全建立卵巢移植供体模型的研究  

Establishment of ovarian transplantation rat model of premature ovarian insufficiency induced by cyclophosphamide

作　　者：丁岩 邵佳亮[2] 李珺玮 张英 华克勤 王翔[2] DING Yon;SHAO Jialiong;LI Junwei;ZHANG Ying;HUA Keqin;WANG Xiong(Deportmentof Gynecology,Obstetrics and Gynecology Hospital,Fudon University,Shanghai 200090,China)

机构地区：[1]复旦大学附属妇产科医院妇科,上海200090 [2]上海交通大学附属第一人民医院泌尿外科

出　　处：《上海医学》2018年第8期483-488,共6页Shanghai Medical Journal

基　　金：国家重点基础研究发展计划(973计划;2011CB944503)

摘　　要：目的探索建立化学治疗(以下简称化疗)所致卵巢功能损伤大鼠模型的适宜方法和最佳时间,为后续卵巢移植治疗提供实验基础。方法将60只成熟雌性Lewis大鼠随机分为3组,每组20只。高剂量组和低剂量组大鼠均腹腔注射环磷酰胺,首次负荷剂量均为50mg/kg,之后每天分别以8和6mg/kg的维持剂量连续注射14d;对照组连续注射0.9%氯化钠溶液1mL共15d。分别于化疗前、化疗结束时、化疗后1和2周,观察大鼠的一般情况、动情周期,测定大鼠生殖内分泌激素水平和丙氨酸转氨酶(ALT)水平;化疗后2周观察卵巢组织形态学变化。结果对照组大鼠一般情况好,体重正常增长。低剂量组和高剂量组大鼠在化疗期间进食减少,活动减少,体毛黯淡。低剂量组大鼠在化疗结束时的体重显著低于对照组同时间(P<0.01);在化疗后1和2周的体重均显著高于同组化疗结束时(P值均<0.01),但仍显著低于对照组同时间(P值均<0.05)。高剂量组大鼠在化疗结束时的体重显著低于同组化疗前和对照组、低剂量组同时间(P值分别<0.05、0.01);在化疗后1和2周的体重均显著高于同组化疗结束时(P值均<0.05),但仍显著低于对照组、低剂量组同时间(P值均<0.01)。对照组大鼠化疗前后动情周期的差异均无统计学意义(P值均>0.05)。低剂量组和高剂量组大鼠在化疗结束时和化疗后2周的动情周期均显著长于同组化疗前和对照组同时间(P值均<0.05),高剂量组大鼠在化疗后2周的动情周期又显著长于低剂量组同时间(P<0.05)。化疗前,3组大鼠各生殖内分泌激素水平的差异均无统计学意义(P值均>0.05)。在化疗结束时,低剂量组和高剂量组大鼠的雌二醇、孕酮、抗苗勒管激素(AMH)水平均显著低于对照组同时间(P值分别<0.05、0.01),高剂量组大鼠的卵泡刺激素(FSH)水平显著高于对照组同时间(P<0.05)。在化疗后1周,低剂量组大鼠的FSH水平显著高于对�Objective To explore an applicable method and optimal time in establishment of rat model of cyclophosphamide （CTX） induced premature ovarian insufficiency （POI）, which is opt to treatment by whole ovarian transplantation. Methods Sixty female Lewis rats were divided into three groups （n =20）： control group （with saline）, low-dose CTX group （CTX 6 mg/kg） and high-dose CTX group （CTX 8 mg/kg）. CTX at a loading dose of 50 mg/kg was intraperitoneally injected on the first day, which was followed by a maintenance dose of 8 mg/kg and 6 mg/kg in high- and low-dose CTX groups, respectively. Normal saline （1 mL） was given in control group for 15 d. The changes of general state, estrous cyclicity, reproductive and endocrine hormones, and alanine aminotransferases （ALT） were observed before chemotherapy, at the end of chemotherapy, one and two weeks after chemotherapy. The changes of morphological ovarian tissue were observed two weeks after chemotherapy. Results In the control group, the general state of rats was good with the body weight increasing normally. CTX induced decreased food intake and activity with dim hair of the rats during chemotherapy. The weight of rats in the low-dose CTX group was significantly lower than that in the control group at the end of chemotherapy （P〈0.01 ）. The weight of rats in the low-dose CTX group increased significantly after one week and two weeks of chemotherapy （both P〈0.01 ）, but it was still significantly lower than that in the control group （both P〈0.05）. The weight of rats in the high-dose CTX group at the end of chemotherapy was significantly lower than that in the cQntrol group and in the low-dose CTX group （P〈0.05, 0.01）. After one week and two weeks of chemotherapy, the weight of rats in the high-dose CTX group increased significantly （both P〈0.05）, but it was still significantly lower than that in the control group and low-dose CTX group （both P〈0. 01 ）. There were no significant differences in estrous cycle

关 键 词：环磷酰胺 模型 动物 大鼠 卵巢功能损伤 化学治疗 

分 类 号：R71[医药卫生—妇产科学] R-332[医药卫生—临床医学]