论文部分内容阅读
[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(P>0.05)。(2)300 mg/kg组大鼠肝脏脏器系数升高(P<0.05),其余剂量组均无统计学差异(P>0.05);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(P>0.05)。(3)DEHP暴露18周后,300 mg/kg大鼠空腹血糖升高(P<0.05),其他时点各组差异均无统计学意义(P>0.05);各组HOMA-IR、ISI、血清胰岛素水平差异均无统计学意义(P>0.05)。(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。
[Objective] To observe the effect of low-dose chronic exposure of di-2-ethylhexyl phthalate (DEHP) on glucose metabolism in female rats. [Methods] 24 SPF female SD rats were randomly divided into 4 groups, which were 0, 3, 30, 300 mg / kg DEHP exposure group, Feeding the way continuous exposure to 46 weeks, regular measurement of fasting blood glucose in rats, and record weight changes. The rats were weighed after the last exposure for 24 h. The oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed respectively. The area under the curve (AUC) was calculated. After chloral hydrate anesthesia, The liver, pancreas, white fat around the genitals, gastrocnemius muscle were weighed and stored in 10% (volume fraction) neutral formalin for histopathological observation (excluding gastrocnemius muscle). [Results] During the course of DEHP exposure, no obvious toxicity was observed in all the rats in each group. Compared with 0 mg / kg group: (1) The weight of rats in each experimental group had no significant difference (P> 0.05). (2) The liver organ coefficient of 300 mg / kg group increased (P <0.05), while the other dose groups had no significant difference (P> 0.05). The white fat and gastrocnemius organ index of pancreas and genitals in each experimental group There was no significant difference (P> 0.05). (3) After 18 weeks of DEHP exposure, the fasting blood glucose in 300 mg / kg rats increased (P <0.05), but there was no significant difference in other groups (P> 0.05). The HOMA-IR, ISI, Serum insulin levels were no significant difference (P> 0.05). (4) The results of OGTT showed that peak blood glucose concentration peaked at 15 minutes (P = 0.004) in female rats at 300 mg / kg and decreased at 60,120 minutes (P = 0.038, P = 0.039). The blood sugar level was lower than the fasting level at 120 min after oral administration of sugar and the blood glucose AUC was decreased (P = 0.040). The ITT results showed that the blood glucose level of 30 mg / kg group was significantly lower than 0 (P = 0.029, P = 0.029). The blood glucose level of 300 mg / kg group decreased significantly at 60 and 120 min, and the blood glucose level decreased more than 50% (P = 0.017, P = 0.038) Slow blood glucose levels, blood glucose AUC decreased 300 mg / kg group (P = 0.028). The results of liver pathology showed that hepatocytes in DEHP-treated rats increased in varying degrees, with edema and interstitial loosening, showing different degrees of biliary peritonitis. Pancreatic histopathology results showed that the islet area of each DEHP-treated group decreased and the number of cells decreased. The histopathology of white adipose tissue around the genitals showed that the adipocytes of various DEHP-treated rats were reduced to varying degrees, the sizes were different, and the cells arranged irregularly. [Conclusion] Chronic exposure to low doses of DEHP may lead to insulin resistance in female rats.