大、小鼠吸收和代谢双酚A的差异
대、소서흡수화대사쌍분A적차이
The differences in absorption and metabolism of bisphenol A between rats and mice
  • 万方数据
    中华预防医学杂志 중화예방의학잡지
    CHINESE JOURNAL OF
    2010年 8期 731-735 ,共5页

    黄春妍%姚陈娟%鞠晶昀%潘少聪%任飞林%陈刚

    황춘연%요진연%국정윤%반소총%임비림%진강

    酚类%大鼠%小鼠%肠吸收%代谢 酚類%大鼠%小鼠%腸吸收%代謝
    분류%대서%소서%장흡수%대사
    Phenols%Rats%Mice%Intestinal absorption%Metabolism
    目的 探讨相同剂量双酚A(bisphenol A,BPA)经口染毒后,引起大、小鼠血清BPA浓度差异的机制.方法 无特定病原体(specic pathogen free,SPF)级雄性SD大鼠和ICR小鼠各18只,一次性经口给予300 mg/kg的BPA后,在第0.5、1.0、12.0小时时间点各采集6只大、小鼠血液,用荧光-高效液相色谱法(fluorescence-high performance liquid chromatography,FL-HPLC)检测血清中BPA浓度;大、小鼠各6只采用原位小肠吸收模型循环灌流100 ml 0.1 mmol/L BPA灌流液,用FL-HPLC法分别检测第0.5、1.0、2.0小时时间点灌注液中BPA浓度和灌流后2.0 h血清中的浓度;采用逆转录PCR(RT-PCR)方法检测大、小鼠肝脏尿苷二磷酸葡萄糖醛酸转移酶2B1(UDP-glucuronosyltransferase 2B1,UGT2B1)mRNA的表达水平,并采用FL-HPLC法检测UGT2B1的酶活性;大、小鼠各6只禁食24 h后,一次性经口给予300 ms/kg BPA,收集24 h粪便,用FL-HPLC法检测粪便中BPA含量.结果 300 ms/kg BPA经口染毒后第0.5、1.0、12.0小时时间点小鼠血清中BPA浓度分别为(66.57±14.95)、(51.16±16.06)、(22.73±5.00)μg/ml,大鼠血清中BPA浓度分别为(15.63±5.65)、(18.34±5.02)、(7.65±2.58)μg/ml,各时间点小鼠均高于大鼠,差异有统计学意义(F值分别为50.660,17.957,8.420,P值均＜0.05);0～、0.5～、1.0～2.0 h小鼠小肠各时间段吸收速率分别为(10.20±4.20)、(1.49±0.67)、(1.31±0.55)μg·cm-2·min-1均高于大鼠相应时间段吸收率[(1.87 ± 0.69)、(0.47±0.13)、(0.36 ± 0.08)μg·cm-2·min-1],差异均有统计学意义(F值分别为14.954、8.877、11.536,P值均＜0.05).0.1 mmol/L BPA灌肠2 h后小鼠血清中的BPA浓度为(22.64±4.35)μg/ml,高于大鼠的(4.13±0.83)μg/ml,差异有统计学意义(F=74.643,P=0.000);大鼠肝脏中BPA代谢酶UGT2B1 mRNA的表达水平和酶活性明显高于小鼠;300 mg/kg BPA经口染毒24 h后,大鼠经粪便排出的BPA量为(1.50±0.32)mg/g,高于小鼠的(0.57±0.35)ms/g,差异有统计学意义(F=21.215,P=0.001).结论 大、小鼠经口给予300 mg/kg BPA染毒后,由于小鼠肠吸收BPA的能力高于大鼠,而大鼠代谢及排出BPA能力高于小鼠,引起小鼠血清中BPA的浓度明显高于大鼠.
    목적 탐토상동제량쌍분A(bisphenol A,BPA)경구염독후,인기대、소서혈청BPA농도차이적궤제.방법 무특정병원체(specic pathogen free,SPF)급웅성SD대서화ICR소서각18지,일차성경구급여300 mg/kg적BPA후,재제0.5、1.0、12.0소시시간점각채집6지대、소서혈액,용형광-고효액상색보법(fluorescence-high performance liquid chromatography,FL-HPLC)검측혈청중BPA농도;대、소서각6지채용원위소장흡수모형순배관류100 ml 0.1 mmol/L BPA관류액,용FL-HPLC법분별검측제0.5、1.0、2.0소시시간점관주액중BPA농도화관류후2.0 h혈청중적농도;채용역전록PCR(RT-PCR)방법검측대、소서간장뇨감이린산포도당철산전이매2B1(UDP-glucuronosyltransferase 2B1,UGT2B1)mRNA적표체수평,병채용FL-HPLC법검측UGT2B1적매활성;대、소서각6지금식24 h후,일차성경구급여300 ms/kg BPA,수집24 h분편,용FL-HPLC법검측분편중BPA함량.결과 300 ms/kg BPA경구염독후제0.5、1.0、12.0소시시간점소서혈청중BPA농도분별위(66.57±14.95)、(51.16±16.06)、(22.73±5.00)μg/ml,대서혈청중BPA농도분별위(15.63±5.65)、(18.34±5.02)、(7.65±2.58)μg/ml,각시간점소서균고우대서,차이유통계학의의(F치분별위50.660,17.957,8.420,P치균＜0.05);0～、0.5～、1.0～2.0 h소서소장각시간단흡수속솔분별위(10.20±4.20)、(1.49±0.67)、(1.31±0.55)μg·cm-2·min-1균고우대서상응시간단흡수솔[(1.87 ± 0.69)、(0.47±0.13)、(0.36 ± 0.08)μg·cm-2·min-1],차이균유통계학의의(F치분별위14.954、8.877、11.536,P치균＜0.05).0.1 mmol/L BPA관장2 h후소서혈청중적BPA농도위(22.64±4.35)μg/ml,고우대서적(4.13±0.83)μg/ml,차이유통계학의의(F=74.643,P=0.000);대서간장중BPA대사매UGT2B1 mRNA적표체수평화매활성명현고우소서;300 mg/kg BPA경구염독24 h후,대서경분편배출적BPA량위(1.50±0.32)mg/g,고우소서적(0.57±0.35)ms/g,차이유통계학의의(F=21.215,P=0.001).결론 대、소서경구급여300 mg/kg BPA염독후,유우소서장흡수BPA적능력고우대서,이대서대사급배출BPA능력고우소서,인기소서혈청중BPA적농도명현고우대서.
    Objective To investigate the mechanism of the different levels of serum bisphenol A(BPA) between rat and mouse after oral administration. Methods A total of 18 specific pathogen free(SPF) male rats and 18 mice were treated with 300 mg/kg BPA by oral administration,blood samples were taken from rats and mice after BPA administration at 0.5,1.0,12.0 h time points(n =6 at each point).Serum BPA levels were quantified using fluorescence-high performance liquid chromatography (FL-HPLC)analysis. The rats and mice (n = 6, respectively ) were perfused with 100 ml of 0.1 mmol/L BPA by intestinal absorption in situ,then the BPA levels of perfusion fluid at 0.5,1.0,2.0 h time points and serum at 2.0 h after BPA perfusion were determined by FL-HPLC analysis. The levels of UDP-glucuronosyltransferase 2B1 ( UGT2B1 ) mRNA expression in the liver of rats and mice were analyzed by semi-quantitative RT-PCR and UGT2B1 enzymatic activity was determined by FL-HPLC method. The rats and mice (n = 6,respectively) were treated with 300 mg/kg BPA by omal administration after fasting 24 h,the feces were collected during 24 h and the levels of BPA in feces were determined by FL-HPLC analysis. Results At 0.5,1.0,12.0 h after oral administration at 300 mg/kg BPA, the levels of serum BPA in mice ( (66.57 ± 14.95 ), ( 51.16 ± 16.06 ), ( 22.73 ± 5.00 ) μg/ml, respectively) were significantly higher than in rats ( ( 15.63 ± 5.65 ), ( 18.34 ± 5.02 ), (7.65 ± 2.58 ) μg/ml, respectively) (F values were 50.660,17.957,8.420,respectively,P ＜ 0.05) ,the rates of absorption in mice small intestine during 0 h -,0.5 h- ,1.0-2.0 h ((10.20 ±4.20),(1.49 ±0.67),(1.31 ±0.55) μg · cm-2 · min-1 ,respectively)were higher than that in rats ((1.87 ±0.69),(0.47 ± 0.13),(0.36 ±0.08) μg · cm-2 · min-1,respectively) ( F values were 14.954,8.877,11.536, respectively, P ＜ 0.05 ), the serum BPA levels in mice( (22.64 ±4.35) μg/ml) were significantly higher than in rats ( (4.13 ±0.83) μg/ml) after 2 h perfusion with 0.1 mmol/L BPA (F = 74.643, P = 0.000), the levels of UGT2B1 mRNA expression and enzymatic activity in the rats liver were obviously higher than in the mice liver. After oral administration at 300 mg/kg BPA,the feces BPA levels of rats ( ( 1.50 ± 0.32) mg/g) were significantly higher than that of the mice((0.57 ±0.35) mg/g) (F=21.215,P=0.001) during 24 h. Conclusion The serum BPA level of mouse is significantly higher than the rat after oral administration at 300 mg/kg BPA, which may be caused by BPA high absorption rate of mouse small intestine and strong ability of BPA glucuronidation and excretion of the rat.
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