DEHP对宫内仔鼠睾酮水平、IGF-1和StAR mRNA表达的影响  

Effect of DEHP on the level of serum testosterone and the expressions of IGF-1 and StAR in testis of intrauterine fetus rat

作　　者：吴亮[1] 王蓉蓉[1] 苏志涛[1] 陈祥义[1] 王环[1] 陈国荣[1] 

机构地区：[1]浙江省温州医学院附属第一医院病理科,温州325000

出　　处：《中国男科学杂志》2010年第9期3-7,共5页Chinese Journal of Andrology

基　　金：国家自然基金资助项目(30671736);温州市科技计划项目(2009H0029)

摘　　要：目的探讨不同剂量的邻苯二甲酸二(乙基)己酯(DEHP)对宫内期仔鼠睾酮水平及胰岛素样生长因子1(IGF-1)、类固醇激素合成急性调节蛋白(StAR)基因表达的影响。方法雌性S-D大鼠24只,随机均分为4组:正常组、低剂量组、中剂量组和高剂量组。后三组给予不同剂量的DEHP灌胃,剂量分别为(1 0mg/kg·d^(-1))、(1 00mg/kg·d^(-1))、和(750mg/kg·d^(-1)),时间自雌鼠怀孕后第一天开始至仔鼠出生后第一天止。正常组给予等剂量的玉米油。测量各组雄仔出生时肛门生殖器距离(AGD)和血清睾酮(T)水平;并用光镜和电镜观察仔鼠睾丸Leydig细胞形态学改变;Real-timePCR检测睾丸组织中IGF-1和StARmRNA表达水平。结果与正常组比较,高剂量组AGD明显缩短,中剂量组AGD呈下降趋势;低剂量组T水平升高、中高剂量组T水平降低;低、中、高剂量组StARmRNA表达下降;低剂量组IGF-1mRNA表达升高,中、高剂量组表达下降。光镜下见随着剂量的升高,睾丸Leydig细胞聚集越明显,高剂量组Leydig细胞呈瘤样聚集;电镜下见低剂量组Leydig细胞线粒体和滑面内质网增多,中、高剂量组均减少,并见脂滴增加。结论 DEHP可以影响宫内仔鼠睾酮的合成,不同剂量具有不同的效应,其机制可能与DEHP影响IGF-1和StARmRNA表达有关。Objective To investigate the effect of different dose of Di（2-ethylhexyl） phthalate （DEHP） on the level of serum testosterone and the expressions of IGF-1 and StAR in testis of intrauterine fetus rat. Methods Twenty-four female Sprague-Dauley rats were randomly divided into four groups including normal control group, low-dose group, middle-dose group and high-dose group. Rats in the latter three groups were gavaged with different dose of DEHP（10mg/kg·d, 100mg/kg · d, 750mg/kg· d） respectively from gestational to postnatal fetus rat on day 1. Rats in normal group were fed withequal dose of corn oil. The indices of angenital distances and serum testosterone were measured respectively. The morphologic changes of Leydig cells were observed by light microscopy and transmission electron microscopy. The mRNA expressions of IGF-1 and StAR in testis were detected by Real-time PCR. Results Compared with that of normal control group, AGD decreased in middle and high dose groups. The level of serum testosterone increased in low dose group whereas decreased in middle and high dose group. The mRNA expression of IGF-1 was upregulated in low-dose group and downregulated in middle and high dose group. The expression of StAR was downregulated in all three groups. The Leydig cells aggregated more obviously under high-dose of DEHP and appeared as the tumor-like aggregation. The number of the endoplasmic reticulum and mitochondrial was increased in Leydig cells in low-dose group and decrease in Leydig ceils in middle and high dose groups. Conclusion The different dose of DEHP might influence the production of serum testosterone in fetus rat, which might be associated with expression level of IGF-1 and STAR.

关 键 词：仔鼠 睾酮 莱迪希细胞 二乙基己基邻苯二甲酸表达 

分 类 号：R996[医药卫生—毒理学] R335.5[医药卫生—药学]