医源性因素早发性卵巢功能不全家兔模型建立  

Establishment of a rabbit model of iatrogenic premature ovarian insufficiency

作　　者：闫丽 金格雅 王恺悦 王喜良 于月新 YAN Li;JIN Ge-ya;WANG Kai-yue;WANG Xi-liang;YU Yue-xin(Department of Reproductive Medicine,General Hospital of Northern Theater Command,Shenyang 110016,China;Graduate School of China Medical University,Shenyang 110122,China)

机构地区：[1]北部战区总医院生殖医学科,辽宁沈阳110016 [2]中国医科大学研究生院,辽宁沈阳110122

出　　处：《临床军医杂志》2024年第1期14-19,共6页Clinical Journal of Medical Officers

基　　金：辽宁省科学技术项目(2020JH2/10300118)。

摘　　要：目的 通过比较不同剂量的环磷酰胺对新西兰白兔卵巢功能的影响,探究建立化疗损伤性早发性卵巢功能不全(POI)家兔模型的最佳给药方案。方法 将32只普通级雌性未交配新西兰白兔随机分入4组,每组各8只。A组为正常对照组;B组50 mg/kg腹腔注射环磷酰胺1 d,8 mg/kg连续注射14 d;C组50 mg/kg连续腹腔注射环磷酰胺3 d;D组100 mg/kg连续腹腔注射环磷酰胺3 d。比较4组家兔的状态、体质量、卵巢长径及卵巢指数;检测4组家兔血清雌二醇和促卵泡生成素水平的变化;HE染色观察4组家兔的卵巢组织形态,统计各级卵泡数量和闭锁卵泡占比;检测4组家兔卵巢组织凋亡相关蛋白Bax和Bcl2蛋白的表达水平。结果 与A组比较,B、C、D组Bax蛋白表达上调(P<0.05),Bcl2蛋白表达下调(P<0.05)。B组原始和初级卵泡数量少于A组,闭锁卵泡数量多于A组,差异有统计学意义(P<0.05)。经腹腔注射环磷酰胺造模3周后,C组和D组家兔体质量低于A组,卵巢长径短于A组,卵巢指数小于A组,雌二醇水平低于A组,促卵泡生成素水平高于A组,原始卵泡、初级卵泡、次级卵泡、窦卵泡数量少于A组,闭锁卵泡数量多于A组,闭锁卵泡占比高于A组,差异有统计学意义(P<0.05)。D组内有2只家兔在给药5 d后死亡。与A组比较,B组家兔体质量、卵巢长径、卵巢指数、激素水平、各级卵泡数量变化差异无统计学意义(P>0.05),提示对卵巢损伤较轻,不适合用于建模。与A组比较,C组和D组家兔体质量、卵巢长径、卵巢指数、激素水平、各级卵泡数量变化差异有统计学意义(P<0.05),但D组卵巢损伤严重,家兔耐受性差,其中2只在给药5 d后死亡,不适合用于造模进行后续研究。结论 50 mg/kg连续腹腔注射环磷酰胺3 d是建立化疗损伤性POI家兔模型的最佳浓度,该方法简便易行,卵巢损伤较稳定,动物耐受性好,能够用于评估POI不同治疗方案的预后效果,为临床研究提�Objective To compare the effects of different doses of cyclophosphamide on ovarian function in New Zealand white rabbits,and to explore the best administration regimen for the establishment of chemotherapy-induced premature ovarian insufficiency(POI)rabbit model.Methods Thirty-two ordinary female unmated New Zealand white rabbits were randomly divided into 4 groups with 8 rabbits in each group.Group A was the normal control group.Group B was intraperitoneally injected with 50 mg/kg cyclophosphamide for 1 day and 8 mg/kg for 14 days.Group C received 50 mg/kg continuous intraperitoneal injection of cyclophosphamide for 3 days.Group D received 100 mg/kg continuous intraperitoneal injection of cyclophosphamide for 3 days.The status,body weight,ovarian length and ovarian index of rabbits in 4 groups were compared.The serum levels of estradiol and follicle-stimulating hormone were detected in 4 groups.HE staining was used to observe the ovarian tissue morphology,the number of follicles at all levels and the proportion of atretic follicles.The expression levels of apoptosis-related proteins Bax and Bcl2 in ovarian tissue of 4 groups were detected.Results Compared with group A,the expression of Bax protein in groups B,C and D was up-regulated(P<0.05),and the expression of Bcl2 protein was down-regulated(P<0.05).The number of primary and primary follicles in group B was less than that in group A,and the number of atretic follicles was more than that in group A,and the difference was statistically significant(P<0.05).After 3 weeks of intraperitoneal injection of cyclophosphamide,the body mass of rabbits in groups C and D was lower than that in group A,the length diameter of the ovary was shorter than that in group A,the ovarian index was lower than that in group A,the level of estradiol was lower than that in group A,the level of follicle stimulating hormone was higher than that in group A,the number of primary follicles,primary follicles,secondary follicles and sinus follicles was lower than that in group A,the number of

关 键 词：早发性卵巢功能不全 环磷酰胺 家兔 动物模型 

分 类 号：R332[医药卫生—人体生理学] R711.75[医药卫生—基础医学]