塑化剂邻苯二甲酸二(2-乙基己)酯对雌性大鼠子宫 组织的毒性作用

目的：探讨塑化剂邻苯二甲酸二（2-乙基己）酯（DEHP）对雌性大鼠子宫组织的影响，阐明DEHP对雌性大鼠子宫毒性作用的机制。方法：将48只成年雌性Wistar大鼠随机分为对照组（给予玉米油）、低剂量DEHP组（300 mg·kg^-1·d^-1DEHP，1/100 LD₅₀）、中剂量DEHP组（1 000 mg·kg^-1·d^-1DEHP，1/30 LD₅₀）和高剂量DEHP组（3 000 mg·kg^-1·d^-1DEHP，1/10 LD₅₀），每组12只。于动情间期处死大鼠，称体质量，计算子宫脏器系数；HE染色法观察各组大鼠子宫组织病理形态表现；免疫组织化学染色法测定各组大鼠子宫组织中卵泡刺激素受体（FSHR）和黄体生成素受体（LHR）表达水平。结果：染毒第2、3、4周，各剂量DEHP组大鼠体质量低于对照组（P<0.05），且呈现明显的剂量-效应关系；各组大鼠子宫脏器系数比较差异无统计学意义（P>0.05）。肉眼可见对照组大鼠子宫形态正常，中和高剂量DEHP组大鼠子宫扭曲、管壁变薄，管腔内有大量黄色或清亮液体，并呈重度扩张；子宫浆膜面可见不同程度的积水、充血和肿胀现象。镜下各剂量DEHP组大鼠子宫内膜出现胞核假复层现象，上皮增生和内皮纤维化，固有层腺体数减少，部分腺体萎缩。与对照组比较，各剂量DEHP组大鼠子宫组织免疫组织化学染色程度逐渐减弱，面积减小。各剂量DEHP组大鼠子宫组织中FSHR表达水平比较差异无统计学意义（P>0.05）。与对照组比较，各剂量DEHP组大鼠子宫组织中LHR表达水平明显降低（P<0.05）；且中和高剂量DEHP组大鼠明显低于低剂量DEHP组（P<0.05）。结论：DEHP可导致雌性大鼠体质量降低，子宫组织发生病理学改变，对雌性大鼠产生子宫毒性作用。

Toxic effect of plasticizer DEHP on uterus tissue of female rats

Objective:To investigate the effect of di(2-ethylhexyl) phthalate (DEHP) on the uterus tissue of female rats, and to clarify the mechanism of uterine toxicity of DEHP in the female rats. Methods:A total of 48 Wistar female rats were randomly divided into control group(given corn oil), low, middle, and high doses of DEHP groups (given 300, 1 000, and 3 000 mg·kg^-1·d^-1 DEHP;1/100,1/30,and 1/10 LD₅₀)(n=12). The rats in various groups were sacrificed during anoestrum, the body weights were recorded and uterine organ coefficients of the rats in various groups were calculated. The pathomorphology of the uterus tissue of the rats in various groups was detected by HE staining. The expression levels of follicle stimulating hormonereceptor (FSHR) and luteinizing hormone receptor (LHR) in uterus tissue of the rats in various groups were detected by immunohistochemistry. Results:Compared with control group, the body weights of the rats in different doses of DEHP groups were decreased (P<0.05) with a dose-effect relationship; there were no significant differences in uterine organ coefficients of the rats in various groups (P>0.05). Macroscopically, the morphology of the uterus of rats in control group was normal; in middle and high doses of DEHP groups, the uterus showed distorted and the tube wall became thinner; different degrees of hydrops, congestion and swelling were seen on the serosal surface of the uterus. The microscopic observation results showed that in different doses of DEHP groups the endometrium nuclei appeared pseudostratified phenomenon; the epithelial hyperplasia and endothelial fibrosis were found in the endometrium; the gland number in the lamina propria was decreased,and part of the glands were depauperate. Compared with control group, the expression levels of FSHR in uterus tissue of the rats in different doses of DEHP groups had no significant differences(P>0.05),and the expression levels of LHR were decreased(P<0.05); the expression levels of LHR in uterus tissue of the rats in middle and high doses of DEHP groups were significantly lower than that in low dose of DEHP group (P<0.05). Conclusion:DEHP can lead to the weight loss and the pathological changes in the uterus tissue of the female rats, and has a uterine toxicity effect on the female rats.