低剂量双酚A灌胃对去卵巢小鼠子宫的增生作用

目的观察小鼠经消化道途径给予低剂量环境内分泌干扰物双酚A对子宫的作用及机制。方法雌性ICR小鼠切除双侧卵巢,恢复性饲养1周,剔除异常个体后,50只动物随机分成5组,每组10只动物,依次皮下注射(sc)10.0μg/(kg·d)17β-雌二醇,灌胃(ig)0、20.0、60.0和180.0μg/(kg·d)BPA,连续7d。动物每3d称量体重一次,于最后一次给药24h后,阴道涂片检测角化上皮细胞,颈椎脱臼处死动物,取子宫,称其干湿重,计算子宫脏器指数,组织切片,HE染色后利用图像分析系统测量子宫上皮高度和宫腔面积。免疫组化法分析子宫雌激素受体(ER)和孕激素受体(PR)表达。结果①与对照组相比,雌二醇和BPA低剂量组动物体重增加,BPA中高剂量组动物体重无明显差异。②阴道涂片结果显示,处于动情期动物数分别为:对照组0/10,雌二醇组10/10,BPA低剂量组2/10,BPA中剂量组1/10,BPA高剂量组0/10;③BPA低剂量组动物子宫湿重和含水量较对照组增加,脏器系数增大,BPA中高剂量组子宫湿重和脏器系数较对照组降低明显(P0.05);④病理组织学及显微图像分析结果显示,BPA低剂量组动物子宫腔面积较对照组增大,中高剂量组子宫腔面积明显减小(P0.01);低剂量组动物子宫上皮高度较对照组增高(P0.01),中高剂量组子宫上皮高度降低明显(P0.01)。⑤免疫组化结果显示,低剂量BPA能增强小鼠子宫ER和PR表达,但随剂量增加,ER表达下降。结论BPA经消化道途径给予ICR小鼠,人环境暴露剂量下具有雌激素活性,但雌激素活性随BPA剂量增大呈现下降趋势。

Proliferative Effect of Intragastrically Administered Low Dose Bisphenol A on the Uterus in Ovariectomized Mice

Objective To investigate the effect and mechanism of low dose bisphenol A（BPA）,a xenoestrogen, given by gastric lavage,on uterus of female mice.Methods Ovariectomized female ICR mice were bred for one week observation and excluding unqualified animals.50 mice were randomly divided into 5 groups,10 animals per group.The mice were administered 10.0 μg /（kg.d） 17β-estradiol（E2 ） by subcutaneous injection and 0,20.0,60.0 or 180.0 μg /（kg.d） BPA via intragastric gavage for 7 days.The body weight was monitored every 3 days,vaginal smears were examined by cytology,and the animals were killed at 24 hours after the last treatment.The uterus was removed to measure the wet weight,water content,and to calculate the organ coefficient.The height of endometrial epithelial cells and luminal area were analyzed with a micro-image analysis system（MIVNT ）.The expression of estrogen receptor（ER ） and progesterone receptor（PR） of uterus were analyzed by immunohistochemistry.Results ①Compared with the control,the mean animal body weights of mice of the E2 group and low dose BPA group were increased,while there were no significiant differences between mid and high dose BPA groups and control.② Based on cytological data of vaginal smear,animal number in estrus were：0 /10 in control group,10 /10 in E2 group,2 /10 in low-dose BPA group,1 /10 in mid-dose BPA group,and 0 /10 in high-dose BPA group.③Compared with the control group,the uterus weight,water content and organ coefficient in the low-dose BPA group were increased,while those of mid-and high-dose BPA groups were significantly decreased（P 0.05）.④ According to the data of histopathology and MIVNT,compared with the control,the uterine luminal area in the low-dose BPA group was significantly enlarged,and the height of endometrial epithelial cells was increased（P 0.01）,while in the mid-and high-dose BPA groups,the luminal area was decreased（P 0.01）,and the height of endometrial epithelial cells was decreased（P 0.01）.⑤ The immunohistochemical data showed that compared with the control group,the ER and PR expressions in the low-dose BPA group were increased,while in the mid-and highdose BPA groups,the expression of ER was decreased,but there were no significant differences.Conclusion A per os intake of BPA at a dose of 20 μg /（kg.d）,a dosage below human daily intake,may promote uterine proliferation in female mice.But this estrogenic activity is decreasing alone with an increasing dose of BPA.