DEHP低剂量慢性暴露对雌性大鼠糖代谢的影响

发布时间：2018-07-06 19:49

本文选题：邻苯二甲酸二(-乙基己基)酯 + 慢性　；参考：《环境与职业医学》2017年08期

【摘要】：[目的]观察邻苯二甲酸二(2-乙基己基)酯(DEHP)低剂量慢性暴露对雌性大鼠糖代谢的影响。[方法]将24只SPF级雌性SD大鼠随机分为4组,分别为0、3、30、300 mg/kg(以体重计,后同)DEHP染毒组,每组6只,采用喂饲的方式连续染毒46周,定期测量大鼠空腹血糖,并记录体重变化。于末次染毒24 h后,称量大鼠体重,分别进行口服葡萄糖耐量试验(OGTT)、胰岛素耐量实验(ITT),计算曲线下面积(AUC);随后水合氯醛麻醉,心尖取血处死,取肝脏、胰腺、生殖器周围白色脂肪、腓肠肌称重,并保存于10%(体积分数)中性福尔马林中固定,用于组织病理形态观察(腓肠肌除外)。[结果]DEHP染毒期间,各组大鼠均未出现明显毒作用表现。与0 mg/kg组比较:(1)各实验组大鼠体重差异均无统计学意义(P0.05)。(2)300 mg/kg组大鼠肝脏脏器系数升高(P0.05),其余剂量组均无统计学差异(P0.05);各实验组胰腺、生殖器周围白色脂肪、腓肠肌脏器系数差异均无统计学意义(P0.05)。(3)DEHP暴露18周后,300 mg/kg大鼠空腹血糖升高(P0.05),其他时点各组差异均无统计学意义(P0.05);各组HOMA-IR、ISI、血清胰岛素水平差异均无统计学意义(P0.05)。(4)OGTT结果显示,雌性大鼠300 mg/kg组服糖后血糖浓度峰值出现早[15 min出现峰值(P=0.004)],而服糖后60、120 min时血糖浓度明显下降(P=0.038,P=0.039),且服糖后120 min血糖浓度低于空腹水平,血糖AUC降低(P=0.040);ITT实验结果显示,30 mg/kg组血糖值在15 min时明显低于0 mg/kg组(P=0.029),300 mg/kg组血糖值下降较为明显,在60、120 min时血糖值下降超过空腹血糖的50%(P=0.017,P=0.038),且恢复至空腹血糖值缓慢,300 mg/kg组血糖AUC降低(P=0.028)。肝脏病理形态结果显示:各DEHP染毒组大鼠肝细胞出现不同程度增大、水肿,间质疏松,可见不同程度胆管周围炎。胰腺病理形态结果显示:各DEHP染毒组大鼠胰岛面积减小、细胞数量减少。生殖器周围白色脂肪病理形态结果显示各DEHP染毒组大鼠脂肪细胞不同程度缩小、大小不一,细胞排列不整齐。[结论]DEHP低剂量慢性暴露可能导致雌性大鼠发生胰岛素抵抗。
[Abstract]:[objective] to observe the effect of low dose chronic exposure of bis (2 ethylhexyl) phthalate (DEHP) on glucose metabolism in female rats. [methods] Twenty-four SPF female Sprague-Dawley rats were randomly divided into 4 groups. The rats in each group were treated with DEHP for 30 300 mg/kg, 6 rats in each group were fed continuously for 46 weeks. Fasting blood glucose was measured regularly and the changes of body weight were recorded. 24 hours after the last exposure, the rats were weighed by oral glucose tolerance test (OGTT), insulin tolerance test (ITT), area under curve (AUC), followed by chloral hydrate anesthesia. White fat around genitalia, gastrocnemius weighing, and fixed in 10% (volume fraction) neutral formalin for histopathological observation (except gastrocnemius). [results] during the period of DEHP exposure, no obvious toxic effect was found in all groups. Compared with 0 mg/kg group: (1) there was no significant difference in body weight of each experimental group (P0.05). (2). The liver organ coefficient of 300 mg/kg group was increased (P0.05), and the other dose groups had no statistical difference (P0.05); the pancreas of each experimental group, white fat around genitalia, white fat around genitalia, There was no significant difference in the organ coefficient of gastrocnemius muscle (P0.05) (P0.05). The fasting blood glucose of rats exposed to DEHP for 18 weeks was increased (P0.05), but there was no significant difference at other time points (P0.05). There was no significant difference in HOMA-IRISI, serum insulin level (P0.05). (4). In female rats, the peak of glucose concentration appeared early after taking glucose for 60120 min (P0. 004), but decreased significantly at 60120 min after taking glucose (P0. 038, P0. 039), and the blood glucose concentration of 120 min was lower than that of fasting after taking glucose. The results of ITT test showed that the blood glucose level of 30 mg/kg group was significantly lower than that of 0 mg/kg group (P0. 029) 30 mg/kg group at 15 min. At 60120 min, the blood glucose decreased by more than 50% of the fasting blood glucose (P0. 017, P0. 038), and recovered to the fasting blood glucose level slowly to the 300 mg/kg group, the blood glucose AUC decreased (P0. 028). The pathological morphology of the liver showed that the liver cells were increased, edema, interstitial looseness and pericholangitis were observed in different DEHP groups. The pancreatic histopathological results showed that the islet area and the number of cells decreased in each DEHP group. The histopathological results of white fat around genitals showed that adipocytes of rats exposed to DEHP decreased to different degrees, size varied, and cells were not arranged neatly. [conclusion] low dose chronic exposure to DEHP may lead to insulin resistance in female rats.
【作者单位】：宁夏医科大学生育力保持教育部重点实验室;宁夏医科大学公共卫生与管理学院劳动卫生与环境卫生学系;宁夏医科大学总医院肿瘤医院病理科;
【基金】：宁夏医科大学2014年中央与地方共建优秀创新团队项目(编号:30100402)
【分类号】：R114

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