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环磷酰胺诱导家兔卵巢早衰动物模型的建立和评价 被引量:14

Establishment and evaluation of a rabbit model of premature ovarian failure induced by cyclophosphamide
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摘要 目的比较不同注药方式下建立环磷酰胺诱导家兔卵巢早衰动物模型的方法,寻找最佳造模方式,为进一步研究卵巢早衰提供更为适用的实验模型。方法 21只家兔随机分四组,正常对照组3只,不作任何处理(A组);模型一组6只,50 mg/kg环磷酰胺溶液注射1 d(B组);模型二组6只,50 mg/kg连续注射2 d(C组);模型三组6只,首日注射50 mg/kg,以后按照8 mg/kg连续注射14 d(D组)。称量各组家兔体重和卵巢重量,描述注药14 d内的体重变化,分析卵巢指数;HE染色观察卵泡形态,光镜下计算各级卵泡数;TUNEL法观察分析细胞凋亡情况;ELISA法分析血清雌二醇(E2)变化。结果体重:B、C组体重无明显变化(P>0.05);D组家兔生长受限(P<0.05),死亡率高。卵巢指数:C组卵巢指数明显小于A组(P<0.05)。各级卵泡情况:B、C组原始卵泡和初级卵泡异常率均升高(P<0.017),其中C组原始卵泡异常率升高更明显(P<0.017),而两组初级卵泡异常率差异无显著性(P>0.017)。A、B、C三组次级、窦状卵泡异常率差异无显著性(P>0.05)。细胞凋亡率:细胞凋亡主要发生在卵泡中的颗粒细胞上,B、C组凋亡率均明显高于A组(P<0.05),且C组凋亡率高于B组(P<0.05)。血清E2值:B组第7天E2分泌达高峰,7 d后逐渐下降,E2分泌量第7天明显高于第35天(P<0.05);C组E2值持续下降,第0天明显高于第35天(P<0.05)。结论以50 mg/kg剂量连续注射2 d是建立环磷酰胺诱导家兔卵巢早衰模型的最佳造模方式。 Objective To compare different regimens of intraperitoneal injection of cyclophosphamide( CTX) to establish a rabbit model of premature ovarian failure( POF),and provide a useful experimental tool for further research of premature ovarian failure. Methods A total of twenty-one 5-6 months old rabbits were randomly divided into 4 groups.The group A( normal control group) included 3 rabbits without any treatment. The group B( the first model group)included 6 rabbits,received a single intraperitoneal injection of 50 mg/kg cyclophosphamide. Six rabbits in the group C( the second model group) were injected with 50 mg/kg cyclophosphamide once daily for 2 days. The group D( the thirdmodel group,also n = 6) was injected with 50 mg/kg cyclophosphamide on the first day and then followed by 8 mg/( kg·d)injection q. d. in the 14 consecutive days. Body weight and ovary weight of the rabbits in each group were measured,and the changes of body weight and the ovary index were analyzed. Morphological changes of the ovarian follicles were observed by HE staining and the numbers of normal and abnormal follicles at different developmental stages were counted and analyzed. Cell apoptosis was analyzed by TUNEL staining and changes in the serum levels of estradiol( E2) were detected by ELISA. Results The body weight of rabbits in both groups B and group C was not significantly changed during the experimental period( P〈0. 05). Rabbits in the group D showed a slight growth( P〈0. 05) and high mortality. The ovary index in group C was significantly lower than that in the group A( P〈0. 05). The ratios of abnormal primordial and primary follicles in groups B and C were significantly increased( P〈0. 017),and the ratio of abnormal primordial follicles in the group C was increased more significantly( P〈0. 017). However,there was no significant difference in the ratios of abnormal primary follicles between groups B and C( P〈0. 017). Among the groups A,B and C,there was no signif
出处 《中国比较医学杂志》 CAS 北大核心 2018年第1期38-43,共6页 Chinese Journal of Comparative Medicine
基金 吴阶平医学基金会临床科研专项资助基金(编号:320.6755.15032) 武汉市应用基础研究计划(编号:20160101010030)
关键词 卵巢早衰 环磷酰胺 动物模型 家兔 premature ovarian failure, POF cyclophosphamide, CTX animal models rabbits
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