环磷酰胺所致卵巢早衰大鼠模型的研究  

The Research on Rat Model of Premature Ovarian Failure Cause by Cyclophosphamide

作　　者：张永芳[1,2] 马会明[1] 王永峰[1,2] 李永丽[1,2] 梁蕾 王燕蓉[1] 裴秀英[1] 徐仙[1,2] 

机构地区：[1]宁夏医科大学生育力保持教育部重点实验室,银川750004 [2]宁夏医科大学总医院生殖医学中心,银川750004

出　　处：《宁夏医科大学学报》2015年第8期874-878,前插1,共6页Journal of Ningxia Medical University

基　　金：国家自然科学基金(81360095)

摘　　要：目的探讨化疗药物环磷酰胺(CTX)致大鼠卵巢早衰(POF)模型的血清生殖激素水平、卵巢细胞凋亡和间质损伤等特征。方法以10周龄雌性SD大鼠为研究对象,以50mg·kg-1的首剂量腹腔注射环磷酰胺,再以8mg·kg-1连续腹腔注射14d,建立POF模型。对照组为未注射CTX的雌性SD大鼠。观察并比较两组大鼠体重、血清激素水平、卵巢组织的形态学改变、卵巢间质损伤程度、卵巢颗粒细胞凋亡蛋白定位及半定量表达。结果 1模型组大鼠注射CTX后体重低于对照组和注射前(P<0.05);2模型组大鼠动情周期紊乱,间期持续或延长;与对照组比较,血清E2及AMH下降,FSH和LH升高(P<0.05);3卵巢间质纤维化,血管标记蛋白CD34染色卵巢血管减少;4模型组大鼠卵巢卵泡颗粒细胞Casepase3、Bax免疫组织化学染色阳性,Bcl-2呈弱阳性;5与对照组比较,模型组卵巢组织Caspase-3蛋白表达升高,Bcl-2蛋白表达降低(P<0.05),Bax蛋白表达两组差异无统计学意义(P>0.05)。结论 CTX致大鼠模型的血清生殖激素异常,卵巢间质纤维化,颗粒细胞凋亡,大鼠卵巢功能过早衰竭。Objective To investigate characteristics of the model that cytoxan( CTX) as a chemotherapeutics drug caused rats' premature ovarian failure( POF). Methods 10-week-old female SD rats were taken as the research objects,and the POF model was established with intraperitoneal injection of 50mg·kg-1CTX as the initial dose and continuous intraperitoneal injection of 8mg·kg-1CTX lasted 14 d. The control group rats were female SD ones without being injected with CTX. Related information was about the two groups of rats,including weight,the level of serum reproductive hormone,morphological changes in ovarian tissue,ovarian interstitial damage degree,protein localization of ovarian granular cell apoptosis and semi-quantitative expression. Results 1Weight of rats in the model group was significantly lower than that of control group and their own weight before injection of CTX( P < 0. 05). 2Rats in the model group showed estrous cycle dysfunction and continuous or prolonged interphase. Compared with those in the control group,rats in the model group had significantly lower serum E2 and AMH,and significantly higher FSH and LH level( P < 0. 05).3Ovarian interstitial fibrosis occured while blood vessel labeled protein CD34 was dyed and ovarian vessels decreased. 4Rats in the model group showed histochemically stainning positive in ovary follicular granulosa cell Casepase3 & Bax immunologic tissue,and Bcl-2 was weakly positive. 5 Compared with those of the control group,rats in the model group had significantly higher Caspase-3 protein expression and lower Bcl-2 protein expression in ovarian tissue( P < 0. 05),while Bax protein expression showed no statistical significance between the two groups( P > 0. 05). Conclusion CTX can cause abnormalities of serum reproductive hormones,ovarian interstitial fibrosis,granular cell apoptosis and POF of rats.

关 键 词：卵巢早衰 生殖激素 凋亡 环磷酰胺 大鼠 

分 类 号：R711.75[医药卫生—妇产科学] R[医药卫生—临床医学]