邻苯二甲酸二丁酯和邻苯二甲酸二(2-乙基己基)酯联合染毒对雌性大鼠的生殖毒性

Combined Toxic Effects of Di-n-butyl Phthalate(DBP)and Di-2-ethylhexyl Phthalate(DEHP)on Reproductive Ability in Female Rats

目的探讨邻苯二甲酸二丁酯(di-n-butyl phthalate,DBP)和邻苯二甲酸二(2-乙基己基)酯(di-2-ethyl hexylphthalate,DEHP)联合染毒对雌性大鼠生育力的影响。方法将32只健康成年清洁级雄性SD大鼠按2×2析因设计随机分为4组,分别为阴性对照(玉米油)组、DBP染毒组(1/20LD50,1.0g/kg)、DEHP染毒组(1/20LD50,1.7g/kg)和DBP(1.0g/kg)+DEHP(1.7g/kg)染毒组,每组8只。采用灌胃方式进行染毒,染毒容量为5ml/kg,每天1次,每周5d,连续染毒8周。末次染毒24h后,测量大鼠体重、肝脏、子宫和卵巢脏器湿重并计算脏器系数。测定血清中氧化损伤指标[超氧化物歧化酶(SOD)活力、还原性谷胱甘肽(GSH)含量、谷胱甘肽过氧化物酶(GSH-Px)活力]、子宫一氧化氮合酶(nitric oxide synthase;NOS)活力和血清中雌性激素[孕酮(P)、雌二醇(E2)、黄体生成素(LH)和促卵泡激素(FSH)]水平,并观察卵巢组织形态学改变和卵巢组织各级卵泡数目。结果 DBP和DEHP联合染毒对雌性大鼠体重增长、子宫系数、血清GSH-Px活力、LH和FSH水平无交互作用;可使卵巢的脏器系数、血清SOD活力、GSH含量、P、E2水平、子宫NOS活力降低,肝脏的脏器系数和闭锁卵泡构成比升高,交互作用均有统计学意义(P<0.05或P<0.01);表现为协同作用。结论 DBP和DEHP联合染毒对雌性大鼠具有明显的生殖毒性作用。

Objective To study the combined toxic effects of di-n-butyl phthalate （DBP） and di-2-ethylhexyl phthalate （DEHP） on reproductive ability of female rats. Methods According to 2×2 factorial analysis, thirty-two healthy and clean adult female SD rats were randomly divided into 4 groups, 8 rats in each group, including one control group （given corn oil） and three experimental groups：DBP （1/20 LD50, 1.0 g/kg, dissolved in corn oil）, DEHP （1/20 LD50, 1.7 g/kg,dissolved in corn oil） and DBP＋ DEHP （1.0 g/kg＋ 1.7 g/kg, dissolved in corn oil）, treated through gavage, once a day, for 8 consecutive weeks. Body weight gain and liver,uterus and ovaries organ weights were determined and the organ coefficient were calculated. The activity of SOD, GSH and GSH-Px in the serum and the activity of nitric oxide synthase （NOS） in the uterus were determined. The level of P, E2, LH and FSH in the serum were determined by radio-immunoassay. The changes of histomorphology in the ovaries and the number of vesicles were observed. Results There was no interaction between DBP and DEHP on the body weight, uterine coefficient, the activities of GSH-Px, LH and FSH in serum; DBP and DEHP obviously induced a decrease in the ovaries organ body weight ratio, the activity of NOS, SOD and the level of GSH in the serum, as well as P and E2 in serum, but an increase in the liver organ body weight ratio and corpora atreticas constituent ratio（P〈0.05 or P〈0.01 ）; there was synergism between DBP and DEHP on the ovaries and liver organ body weight ratio, as well as the activities of SOD and GSH, the level of P and the E2 in serum. There was synergism between DBP and DEHP on the NOS activity in the uterus and the corpora atreticas rate. Conclusion DBP combined with DEHP can cause obvious toxic effects on reproductive function in female rats.