烷化剂联合应用建立小鼠卵巢早衰模型的初步研究

Study of alkylating agents on construction of the premature ovarian failure model

目的探索烷化剂联合应用在构建小鼠卵巢早衰(POF)模型的作用及效果。方法以6～7周龄ICR雌性小鼠为研究对象,造模组(MG)为一次性腹腔注射150 mg·kg-1的环磷酰胺和20 mg·kg-1的白消安,对照组(CG)为同体积溶媒DMSO腹腔注射。通过检测小鼠动情周期、血清FSH和E2水平、早期发育卵泡数的变化及抗苗勒管激素(AMH)和生长分化因子9(GDF9)表达水平变化,以判断造模效果。结果 MG组小鼠动情周期紊乱,POF造模成功率为37.5%,造模60 d后与同期对照组比较模型组小鼠血清FSH显著升高(P<0.05),早期发育卵泡数明显减少(P<0.05),卵巢组织AMH表达减少。结论 150 mg·kg-1的环磷酰胺和20 mg·kg-1的白消安一次性腹腔注射后可引起小鼠卵巢内分泌功能紊乱和卵巢组织的明显损伤,导致卵巢早衰。

Objective To study the function and effect of alkylating agent in construction of premature ovarian failure （POF）. Methods 6 -7 week -old ICR female mice were divided into tow groups： 150 mg · kg^-1 cyclophosphamide and 20 mg · kg^-1 busulfan was administrated with the model group （MG） mice by intraperitoneal injection, the same quantity of DMSO was administrated with the mice in the control group （CG） by intraperitoneal injection. The function of ovary were checked by analyzing estrus cycle ,serum FSH and E2 levels, the number of early developmental follicles, the expression of Anti -MUllerian hormone （AMH） and growth differentiation facter - 9 （GDF9）. Result The estrus cycle of mice was remarkably disordered in the MG and the incidence rate of POF was 37.5% ,the number of early developmental follicles during MG was significantly decreased than that in CG （P 〈 0.05） ,the serum FSH levels in MG during 60 days was higher than that in CG （ P 〈 0.05 ）, the expression level of AMH was remarkably decreased in ovarian tissue of MG. Conclusion It can cause ovarian endocrine dysfunction and ovarian structural damage, as well as POF are caused by co - administrated with 150 mg · kg^-1 cyclophosphamide and busulfan 20 mg · kg^-1.