环磷酰胺下调大鼠睾丸OCT-4和GDNF表达

摘要

目的 探讨抗肿瘤药物环磷酰胺对大鼠睾丸和精原干细胞相关因子OCT-4和GDNF表达的影响.方法 12只8周龄大鼠随机分为对照组和实验组,每组6只；实验组每天腹腔注射环磷酰胺50 mg/kg,连续3d,用药4周后PAS染色法观察大鼠睾丸组织学变化,精原细胞,生精小管直径和附睾尾部精子数量.免疫组织化学法检测精原干细胞相关分子OCT-4和GDNF表达水平.结果 与对照组比较,实验组大鼠体重、睾丸和附睾重量均显著减轻,睾丸组织学无明显改变,附睾精子活动度降低,附睾精子和精原细胞数量减少.实验组GDNF表达明显减少,而OCT-4表达水平无明显变化.结论 环磷酰胺短期用药可造成精子发生的损害,其中精原细胞的减少可能与损害后GDNF表达下调有关.%Objective To observe the effects of cyclophosphamide on the expressions of GDNF and OCT-4 that related functions of spermatogonial stem cells in rats.Methods Twelve 8-week male SD rats were randomly divided into control and experimental group.The rats in experimental group were injected with cyclophosphamide [50 mg/(kg · d)] intraperitoneally for three days.The testis and epididymis were removed after 4 weeks of injection to assess the weight,sperm mobility,sperm and spermatogonia numbers and diameter of seminiferous tubule.The expressions of OCT-4 and GDNF were measured by immunohistochemistry assay.Results Compared with the control group,the weights of testis and epididymis were reduced.Although there was no observed changes of testicular histology,the epididymal sperm mobility,and the numbers of epididymal sperm and spermatogonia were reduced.The expression of GDNF was decreased and that of OCT-4 was not changed.Conclusions The spermatogenesis was damaged by short-term treatment of cyclophosphamide,cyclophosphamide may cause the reduction of spermatogonia through the downregulation of GDNF.