李奕明, 贾福怀, 秦晋, 吴珉, 厉曙光, 陈波. 邻苯二甲酸二(2-乙基)己酯染毒对雄性大鼠胰岛素抵抗及氧化应激的影响[J]. 环境与职业医学, 2019, 36(4): 313-319. DOI: 10.13213/j.cnki.jeom.2019.18646
引用本文: 李奕明, 贾福怀, 秦晋, 吴珉, 厉曙光, 陈波. 邻苯二甲酸二(2-乙基)己酯染毒对雄性大鼠胰岛素抵抗及氧化应激的影响[J]. 环境与职业医学, 2019, 36(4): 313-319. DOI: 10.13213/j.cnki.jeom.2019.18646
LI Yi-ming, JIA Fu-huai, QIN Jin, WU Min, LI Shu-guang, CHEN Bo. Effects of di(2-ethylhexyl) phthalate exposure on insulin resistance and oxidative stress in male rats[J]. Journal of Environmental and Occupational Medicine, 2019, 36(4): 313-319. DOI: 10.13213/j.cnki.jeom.2019.18646
Citation: LI Yi-ming, JIA Fu-huai, QIN Jin, WU Min, LI Shu-guang, CHEN Bo. Effects of di(2-ethylhexyl) phthalate exposure on insulin resistance and oxidative stress in male rats[J]. Journal of Environmental and Occupational Medicine, 2019, 36(4): 313-319. DOI: 10.13213/j.cnki.jeom.2019.18646

邻苯二甲酸二(2-乙基)己酯染毒对雄性大鼠胰岛素抵抗及氧化应激的影响

Effects of di(2-ethylhexyl) phthalate exposure on insulin resistance and oxidative stress in male rats

  • 摘要: 目的 胰岛素抵抗是2型糖尿病和多种慢性代谢性疾病的发病基础,其发生发展与环境因素密切相关。邻苯二甲酸二(2-乙基)己酯(DEHP)作为常见的增塑剂近年来随着塑料制品的广泛应用而在环境中广泛存在,流行病学研究表明DEHP暴露与2型糖尿病及肥胖等慢性疾病相关。本研究观察DEHP染毒对健康雄性大鼠糖脂代谢、胰岛素抵抗及氧化应激水平的影响。

    方法 将24只SPF级健康雄性Wistar大鼠按体重随机分为4组,分别为对照组(玉米油)、DEHP 10 mg/kg组、DEHP 100 mg/kg组、DEHP 1 000 mg/kg组,染毒方式为经口灌胃(5 mL/kg),每日一次,连续染毒30 d。分别于染毒第0、14、28天尾尖采血检测随机血糖,染毒第29天通过口服葡萄糖耐量试验观察大鼠糖耐量变化。末次染毒次日测空腹血糖(FPG),麻醉并处死大鼠后取肝组织称重并计算肝脏脏器系数。全自动生化仪测定血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、碱性磷酸酶(ALP)、白蛋白(ALB)、三酰甘油(TG)水平,放射免疫法测定血清胰岛素(FINS),比色法测定血清游离脂肪酸(FFA)、丙二醛(MDA)、过氧化氢(H2O2)水平。

    结果 DEHP染毒对大鼠体重变化及膳食摄入的影响无统计学意义(P>0.05)。染毒第14天和第28天,DEHP 1 000 mg/kg染毒组与对照组相比随机血糖值升高(P < 0.05)。随DEHP染毒剂量增加,染毒组大鼠葡萄糖耐量曲线血糖峰值升高,各染毒组葡萄糖曲线下面积差异无统计学意义(P>0.05)。与对照组(3.03±0.33)%相比,低、中、高染毒组大鼠肝脏器系数(3.16±0.18)%、(3.68±0.29)%、(5.02±0.46)%均升高(P < 0.05)。与对照组相比,DEHP100 mg/kg、DEHP 1 000 mg/kg组大鼠血清ALB水平升高(P < 0.05);各DEHP染毒剂量组大鼠TG水平均升高(P < 0.05);DEHP 1 000mg/kg染毒组大鼠血清ALP、ALT水平升高(P < 0.05);各DEHP染毒组大鼠血清AST相较于对照组差异无统计学意义(P>0.05)。各DEHP染毒组大鼠FPG、FINS、胰岛素抵抗的稳态模型评估指数相较于对照组大鼠差异无统计学意义(P>0.05)。DEHP 1 000 mg/kg染毒组大鼠血清FFA、H2O2水平较对照组升高(P < 0.05),各染毒组血清MDA水平与对照组相比差异无统计学意义(P>0.05)。

    结论 100~1 000 mg/kg的DEHP染毒可导致雄性Wistar大鼠肝脏损伤,葡萄糖耐量改变,糖脂代谢异常,氧化应激水平升高。

     

    Abstract: Objective Insulin resistance is fundamental to the development of diabetes mellitus type 2 and multiple chronic metabolic diseases, and is closely linked to environmental factors. Di(2-ethylhexyl) phthalate (DEHP) as a common plastcizer has been widely applied in plastc products and thus widely present in environment, while epidemiological studies have shown that DEHP exposure is associated with chronic diseases such as diabetes mellitus type 2 and obesity. This experiment is conducted to observe the toxic effects of DEHP on glycolipid metabolism, insulin resistance, and oxidatve stress in healthy male rats.

    Methods Twenty-four healthy SPF male Wistar rats were randomly divided into four groups by weight, including one control group (corn oil) and three experimental groups treated with 10 mg/kg, 100 mg/kg, and 1 000 mg/kg DEHP by gavage (5 mL/kg), once a day, for 30 consecutve days. Tail venous blood was collected to measure random blood glucose on the 1st, 14th, and 28th days, and the changes of glucose tolerance of rats were observed by oral glucose tolerance test on the 29th day. All rats were detected for fastng plasma glucose (FPG) on the next day of last exposure, and then anesthetzed and sacrifced to weigh liver and calculate liver coefcient. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB), and triglyceride (TG) were determined with auto-biochemical analyzer; the fastng insulin (FINS) was measured by radio-immunological method; the serum levels of free faty acids (FFA), malondialdehyde (MDA), and hydrogen peroxide (H2O2) were determined by colorimetry.

    Results The designed DEHP exposure had no signifcant effect on body weight and food intake of rats (P>0.05). On the 14th and 28th days, the 1000mg/kg DEHP group showed increased random blood glucose compared with the control group (P < 0.05). With the increase of DEHP dose, the peak of glucose tolerance curve was heightened, but no difference in the area under curve of glucose among the groups were observed (P>0.05). Compared with the control group(3.03±0.33)%, the liver coefcients increased signifcantly in the three DEHP exposure groups(3.16±0.18)%, (3.68±0.29)%, and (5.02±0.46)%, respectvely (P < 0.05). The serum levels of ALB in the 100mg/kg and 1000mg/kg DEHP groups were higher than that in the control group (P < 0.05); the serum levels of TG in the groups treated with various doses of DEHP were increased (P < 0.05); the serum levels of ALP and ALT in the 1 000 mg/kg DEHP group were higher (P < 0.05); no difference in serum AST was observed (P>0.05). There were no signifcant changes in FPG, FINS, and index of homeostasis model assessment of insulin resistance afer designed DEHP exposures compared with the control group (P>0.05). The serum levels of FFA and H2O2 of the 1 000 mg/kg DEHP group were signifcantly higher than those of the control group (P < 0.05), but there was no signifcant difference in serum MDA (P>0.05).

    Conclusion DEHP exposure at 100-1 000 mg/kg could lead to liver damage, altered glucose tolerance, glycolipid metabolism disorder, and increased oxidatve stress in male Wistar rats.

     

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