低剂量邻苯二甲酸二(2-乙基)己酯对老年大鼠前列腺的促增生作用

摘要

目的 评价环境暴露剂量的邻苯二甲酸二(2-乙基)己酯(DEHP)对老年大鼠前列腺的促增生作用及机制.方法 32只1.5岁龄老年雄性SD大鼠随机分成4组,每组8只,分别ig给予DEHP(30,90和270 μg·kg-1)或溶媒,每天1次,连续4周.于末次给药24 h后将大鼠麻醉,而后①腹主动脉采血,采用ELISA检测血清中睾酮(T)、雌二醇(E2)和泌乳素(PRL)水平;②处死后取前列腺,分叶,称重、测量体积,计算脏器系数;③制作前列腺组织病理切片,HE染色后用显微镜观察组织形态改变,并利用显微图像分析软件分析前列腺上皮高度变化.结果 与溶媒对照组比较,DEHP 270 μg·kg-1组前列腺系数、背侧前列腺质量和背侧前列腺系数均显著增加(P＜0.05);DEPH各剂量组腹侧前列腺上皮高度明显升高(P＜0.01);DEHP 270 μg·kg-1组背侧前列腺上皮高度明显升高(P＜0.01);DEHP各剂量组E2,PRL和T水平均无显著改变,但DEHP30和270 μg·kg-1组E2/T比值显著增加(P＜0.05).结论 低剂量DEHP对老年大鼠前列腺具有促增生作用,该作用可能与其影响内源性激素的相对水平有关.%OBJECTIVE To investigate the proliferation effect of di(2-ethylhexyl) phthalate (DEHP) on prostate in aged rats at the environmental exposure dose and the possible mechanism.METHODS Thirty-two male Sprague-Dawley rats,aged 1.5 years,were randomly divided into 4 groups (8 rats per group) and treated with DEHP (30,90 and 270 μg· kg-1,ig) and vehicle once daily respectively for 4 weeks.All the animals were anesthetized with pentobarbital sodium and sacrificed on the day subsequent to the last treatment.① Abdominal aortic blood samples were collected,and serum estradiol (E2),testosterone (T) and prolactin (PRL) levels were assayed by ELISA.② The prostate tissues were dissected and categorized into different lobes,weighed and measured.The prostate relative mass was calculated.③ The morphological changes were detected by HE staining and prostate epithelial height was analyzed with microscopic image analysis software.RESULTS Compared with vehicle control group,the prostate relative mass,dorsolateral prostate mass,and dorsolateral prostate index in DEHP 270 μg· kg-1 group were significantly higher (P＜0.05).The height of the ventral prostate epithelium in DEHP 30,90 and 270 μg· kg-1 groups was increased significantly (P＜0.01),so was the height of dorsal prostate epithelium in DEHP 270 μg· kg-1 group (P＜0.01).There were no significant changes in levels of E2,PRL or T in DEHP 30,90 and 270 μg· kg-1 groups,but the ratios of E2/T in DEHP 30 and 270 μμg· kg-1 groups were increased significantly (P＜0.05).CONCLUSION Low-dose DEHP could promote the proliferation of prostatic hyperplasia in the aged rats,which might be associated with the relative levels of endogenous hormone.