摘要
目的探寻维生素E（VitaminE，VitE）对邻苯二甲酸二（2-乙基）己酯[-Di（2-ethylhexyl）phthalate，DEHP]所致大鼠尿道发育毒性的拮抗作用及其可能机制。方法GD12（gestationday12）SD孕鼠随机分为4组，每组20只：玉米油对照组、DEHP组（500mg·kg＾-1·d＾-1）、DEHP（500mg·kg＾-1·d＾-1）＋VitE（200mg·kg＾-1·d＾-1）组和VitE组（200mg·kg＾-1·d＾-1）。各组分别于母鼠孕期12～19d（GDl2～19）持续经口灌注给药。各组分别留取10只孕鼠让其正常分娩，出生第一天，即对新生大鼠计数，并在解剖显微镜下测量雄性新生鼠的肛门生殖器距离（anal genital distance，AGD）并称体重；雄性仔鼠70日龄时逐个检查尿道下裂的发生情况。余孕鼠在GD19d行破宫产取仔代鼠，应用逆转录一聚合酶链反应（RT-PCR）的方法检测胎鼠阴茎TGF-β1，TGF-βR3mRNA的表达水平。DNA末端原位标记染色法（TuNEL法）检测胎鼠阴茎尿道上皮细胞凋亡情况。结果各组TGF-β1mRNA表达水平分别为：正常组为0．63±0．07、DEHP组为0．96±0．12、DEHP＋VitE组为0．65±0．07、VitE组为0．62±0．06，DEHP组表达明显较其他各组增高（P〈0．05）。各组TGF-13R3mRNA表达水平分别为：正常组为0．47±0．10、DEHP组为0．75±0．10、DEHP＋VitE组为0．49±0．09、VitE组为0．46±0．09，DEHP组表达明显较其他各组增高（P〈0．05）。各组胎鼠阴茎凋亡指数分别为：正常组为（30±2．O）％、DEHP组为（8．8±1．1）％、DEHP＋VitE组为（28．9±1．6）％、VitE组为（29．6±2．0）O，DEHP组凋亡细胞数较其他各组相比明显减少，差异有统计学意义（P〈0．01）。导致大鼠尿道下裂的发生。VitE可降低DEHP上调的胎鼠阴茎TGF-β，TGF-β3 mRNA表达水平，恢复胎鼠阴茎尿道上皮细胞的凋亡水平。结论VitE对DEHP所致尿道发育毒性具有拮抗作用，其机制可能与调控TGF-βs及胎鼠阴茎尿道上皮
Objective To study the therapeutic effects of Vitamin E （VitE） on urethral develop-ment toxicity induced by di（2-ethylhexyl） phthalate （DEHP）. Methods From gestational day 12 to gestational day 19 （GD 12-19） , the timed-pregnant Sprague-Dawley （SD） rats were fed with the ei- ther DEHP （500 mg· kg^-1. d ^-1 ）, or VitE （200 mg ·kg^-1. d^-1 ）, or DEHP （500 mg· kg^- 1· d^-1 ） ＋ VitE （200 mg· kg^-1· d^-1） by gastric gavage. According to the treatment, the rats were divided into 4 groups with 20 in each group： DEHP group, DEHP ＋ VitE group, and VitE group. The control rats were fed with corn oil. Ten pregnant rats of each group delivered full-term infant rats. The male infant rats were counted, and the anal genital distance （AGD） and body weight were measured. Hypospadias morbidity was also counted on male rats after 17 postnatal days. In the rest 10 pregnant rats of each group, fetuses were harvested on GD19. Semi-quantitive RT-PCR was used to measure mRNA ex- pression of TGF-β1 and TGF-βR3. TUNEL staining was used to measure cell apoptosis in the fetus＇ genital tubercles. Results Hypospsdias was observed in male rat after 17 postnatal days. The TGF-β1mRNA of the control group, DEHP group, DEHP ＋ VitE group, and VitE group is 0. 63 ± 0. 07, 0. 96 ± 0. 12, 0. 65 ±0. 07, and 0. 62 ± 0. 06, respectively. The TGF-βR3 mRNA of the control group, DEHP group, DEHP ＋ VitE group, and VitE group was 0. 47 ± 0. 10, 0. 75 ± 0. 10, 0. 49± 0. 09, and 0. 46 ±0. 09, respectively. The TGF-β1 mRNA and TGF-βR3 mRNA was up-regulated in the fetus of DEHP group （P〈0. 05）. Cell apoptosis rate in fetus＇ genital tubercles on GD19 of the control group, DEHP group, DEHP ＋ VitE, and VitE group was 30% ±2. 0%, 8. 8%±1.1%, 28. 9%±1.6%, and 29. 6% ±2. 0%, respectively. Cell apoptosis rate was significantly reduced in the fetus of DEHP group （P〈0. 01）. In the GD19 fetus treated with VitE, hypospadias morbidity, the TGF-β1 and TGF-βR3 mRNA expressions were si
出处
《中华小儿外科杂志》
CSCD
北大核心
2011年第8期616-621,共6页
Chinese Journal of Pediatric Surgery
基金
科技部十一五科技支撑计划（编号：2006BA105A06）
国家自然科学基金（编号：81070475）
