基于尿苷二磷酸葡萄糖醛酸转移酶1解毒通路探讨枸杞汁对邻苯二甲酸二(2-乙基己基)酯代谢的干预作用

摘要

目的:通过大鼠毒性干预实验观察枸杞汁对邻苯二甲酸二(2-乙基己基)酯(di-(2-ethylhexyl) phthalate, DEHP)染毒大鼠肝脏中尿苷二磷酸葡萄糖醛酸转移酶1(uridine diphosphate glucuronosyltransferase 1,UGT1)活性及代谢解毒的影响,探讨枸杞汁对DEHP代谢的干预效果.方法:60 只雄性大鼠随机分为对照组、DEHP组和枸杞汁干预组,每组20 只,DEHP组和干预组在DEHP一次染毒(3000 mg/kg mb)后连续7 d分别灌胃生理盐水和枸杞汁,对照组则给予同等体积的芝麻油或生理盐水,期间每天收集大鼠24 h尿液.在染毒1、3、5、7 d后各组分别随机处死5 只.采用试剂盒检测肝脏UGT1的活力,高效液相色谱法检测血清中的邻苯二甲酸单(2-乙基己基)酯(mono-(2-ethylhexyl) phthalate,MEHP)以及尿液MEHP和邻苯二甲酸(phthalic acid,PA)含量.结果:枸杞汁干预组大鼠第5天UGT1活性显著高于DEHP组和对照组(P<0.05),且相对于DEHP组血清中MEHP含量减少而尿液中MEHP和PA含量增加.结论:枸杞汁可能通过提高UGT1活力促进了DEHP的代谢与排泄,发挥了解毒效应,将来可能作为一种预防或对抗邻苯二甲酸酯类物质或其他有毒化学物潜在危害的保健药材或功能食品用于人群的健康防护.%Purpose: This study aimed to explore the intervention effect of Lycium barbarum juice (LBJ) on the metabolism of di-(2-ethylhexyl) phthalate (DEHP) by analyzing the activity of uridine diphosphate glucuronosyltransferase 1 (UGT1) and metabolic detoxification profile in the liver of rats exposed to DEHP. Methods: Sixty Sprague Dawley male rats were randomly divided into three groups (n = 20 each): control group, DEHP group and LBJ group. The DEHP and LBJ groups were administered with normal saline and LBJ respectively by gavage once daily for 7 consecutive days after receiving a single dose of 3 000 mg/kg mb DEHP dissolved in sesame oil. The control group was treated with normal saline for 7 days after receiving the same volume of sesame oil of. Urine samples were collected for 24 hours daily during the experimental period. Totally 5 rats were sacrificed randomly in each group after 1, 3, 5 and 7 days of exposure. The activity of UGT1 was determined by an enzyme linked immunosorbent assay kit while the contents of mono-(2-ethylhexyl) phthalate (MEHP) in serum and urine and phthalic acid (PA) in urine were detected by high performance liquid chromatography. Results: The activity of UGT1 in the LBJ group significantly increased on the 5th day compared to the DEHP and control groups (P < 0.05).The content of serum MEHP in the LBJ group decreased significantly, whereas the contents of urine MEHP and PA increased compared to DEHP group. Conclusion: LBJ can promote the metabolism and excretion of DEHP through improving the activity of UGT1, making it a healthcare product or functional food against the potential hazard of phthalate esters (PAEs) or other poisonous chemicals.