邻苯二甲酸二(2-乙基己)酯对小鼠睾丸损伤及 p-CREB蛋白 表达的影响

目的：探讨邻苯二甲酸二（2-乙基己）酯（DEHP）对小鼠睾丸损伤及睾丸组织磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）表达的影响。方法：选用ICR初断乳雄性小鼠40只，随机分为对照组（玉米油）和DEHP染毒组（250、500、1 000 mg/kg），经口灌胃，1次/天，6天/周，连续8周，于末次染毒24 h后处死动物，称取睾丸、附睾质量计算脏器系数并进行精子计数，检测睾丸组织形态学改变，采用免疫组织化学SP法检测睾丸组织p-CREB蛋白的表达。结果：与对照组相比，250、500和1 000 mg/kg DEHP染毒组小鼠附睾脏器系数及精子计数均明显降低（P < 0.05），1 000 mg/kg组小鼠睾丸系数亦明显下降，差异有统计学意义（P < 0.05）。各DEHP染毒组小鼠睾丸曲细精管上皮细胞出现层次减少、排列疏松、紊乱等改变；随着染毒剂量升高，睾丸组织中p-CREB蛋白表达下降，DEHP 500和1 000 mg/kg组较对照组差异有统计学意义（P < 0.05）。结论：DEHP可致小鼠曲细精管生精上皮细胞损伤、精子数下降、p-CREB蛋白表达减少。

Effects of di-(2-ethylhexyl) phthalate on testicular injury and on expression of p-CREB in testes of mice

OBJECTIVE:To investigate the effects of di-(2-ethylhexyl)phthalate (DEHP) on spermatogenic function and expression of p-CREB in testes of mice. METHODS:40 newly weaned ICR male mice were treated with DEHP by gavage in doses of 0,250,500,1 000 mg/kg,6 times a week for 8 consecutive weeks. The weights of testes,epididymis and sperm counts were determined. Histomorphology and expressions of p-CREB of testicle tissues were also analyzed. RESULTS:Results:Compared with the control group,the epididymis coefficient and sperm counting of DEHP treated groups were all reduced significantly (P < 0.05). The testicular coefficients were also decreased in the 1000 mg/kg group (P < 0.05). Pathological alterations of testes were also observed. Reduced seminiferous epithelium,loose and anomalistic organization were observed in all treatment groups. Sperm counts were reduced in the lumina of seminiferous tubules. p-CREB protein expressions were down-regulated in the 500 and 1 000 mg/kg exposure groups (P < 0.05). CONCLUSION:Our data show that exposure in mice to DEHP damaged epithelial cells of seminiferous tubule,decreased the number of spermatozoa and the expression of p-CREB protein.