环磷酰胺对雄性大鼠生殖免疫功能的影响

目的观察环磷酰胺对大鼠睾丸及其细胞免疫的影响,探讨抗肿瘤药物在生殖免疫功能中的机制。方法选用16只15周龄SD大鼠,随机分为对照组和实验组,每组8只;实验组腹腔注射环磷酰胺20mg/kg/d,连续5天,用药两个月后,应用HE染色法研究大鼠睾丸远期组织学变化,用原位缺口末端标记法（TUNEL方法）检测生精小管中生殖细胞凋亡,放射免疫法检测血清睾酮（T）、卵泡刺激素（FSH）、黄体生成素（LH）,流式细胞术进行血液T淋巴细胞亚群分析。结果实验组睾丸生精小管直径缩小、间距增宽、生精上皮变薄、生殖细胞层次和数量减少、生精小管腔多未见精子形成,实验组睾丸生精小管直径、面积、生殖细胞数均显著低于对照组（P〈0.01）;实验组与对照组比较生殖细胞凋亡增多,差异显著（P〈0.01）;实验组与对照组比较血清T明显降低,差异显著（P〈0.01）,血清FSH、LH水平两组间差异无显著性;血液T淋巴细胞亚群分析,实验组与对照组比较CD3＋CD4＋、CD4＋/CD8＋明显降低（P〈0.01）,CD3＋CD8＋明显升高（P〈0.01）。结论环磷酰胺对大鼠睾丸远期损害明显,促进生殖细胞凋亡,降低睾酮的分泌,并抑制T淋巴细胞的免疫功能。

The Effect of Cyclophosphamide on the Reproductive Immunity of Male Rats

Objective To investigate the toxic effects of cyclophosphamide(CP) on the testis and the cellular immunity of rats.Methods Sixteen 15-week male SD rats were randomly divided into a control and an experimental group.The rats of the experimental group were injected intraperitoneally with cyclophosphamide of 20 mg/kg/d×5d.After 2 months,the histological changes were examined by light microscopy.The testicular germ cell apoptosis was visualized by TUNEL.Serum testosterone(T),follicle-stimulating hormone(FSH),and luteinizing hormone(LH) levels were detected by radioimmunoassay.Flow Cytometry analysis was used to detect blood T-lymphocyte subsets.Results The average diameter and area of seminiferous tubules,and the cell number of spermatogenic epithelium in the experimental group were all lower than those in controls(P<0.01).The spermatozoon was not found in many the seminiferous tubules.The experimental group showed obvious increase of germ cell apoptosis in testicular seminiferous tubules compared with the control group(P<0.01).Serum T of the experimental group was significantly decreased(P<0.01).There was no significant difference in serum FSH and LH levels between these groups.Compared with those of the control group,CD3+/CD4+ and CD4+/ CD8+ were decreased significantly(P<0.01)and CD3+/CD8+ increased significantly higher(P<0.01) in the experimental group.Conclusion The toxic effects of cyclophosphamide on rat testis are obvious.The germ cell apoptosis is significantly increased.Testosterone secretion of Leydig cells and T lymphocyte immunity are inhibited.