孕鼠围产期全氟辛烷磺酸盐暴露对新生幼鼠发育的影响及机制研究

Effect of perfluorooctane sulfonate exposure in perinatal period of pregnant rats on the development of newborn pups and its mechanism

目的研究孕鼠围产期全氟辛烷磺酸盐(PFOS)暴露对新生幼鼠生长发育的影响及其可能的作用机制。方法选取无特定病原体(SPF)级SD大鼠60只,其中雄性大鼠20只,雌性40只,体重(200±20)g,由南京青龙山动物繁殖场提供。适应性饲养1周后,选取20只孕鼠按照随机数字表法分为对照组和PFOS组,每组10只。PFOS组孕鼠每天灌胃1.5 mg·kg^(-1)·d^(-1)的PFOS溶液,对照组每天灌胃等体积的0.05%Tween-20溶液,直至幼鼠出生后第21天。监测幼鼠体重变化;分别于幼鼠出生后的第0天和第21天,采用高效液相色谱-质谱(HPLC-MC)测定血清和肝组织中PFOS的含量;于第12周时称重并处死所有幼鼠,分离心脏、肝脏、脾脏、肺、肾脏、脑组织,称重并计算脏器系数;采用酶联免疫吸附试验(ELISA)法测定孕鼠血清糖皮质激素(GC)和幼鼠血清胰岛素样生长因子-1(IGF-1)的表达水平。结果哺乳期PFOS幼鼠的体重均低于同期对照组幼鼠,差异有统计学意义(P<0.05);自断乳至6周龄时,PFOS组幼鼠的体重均显著低于对照组,差异有统计学意义(P<0.05);自9周龄开始,两组幼鼠的体重差异无统计学意义(P>0.05)。第0天和第21天时,PFOS组幼鼠血清及肝组织中均高表达PFOS;与第0天时相比,第21天时PFOS组幼鼠血清和肝组织中的PFOS的浓度均显著升高,差异均有统计学意义(P<0.05)。与对照组幼鼠相比,PFOS组幼鼠的心脏质量和心脏系数较低,肝脏质量和肝脏系数较高,差异均有统计学意义(P<0.05)。与对照组相比,PFOS组孕鼠血清GC水平显著升高,而IGF-1的表达水平显著降低,差异均有统计学意义(P<0.05)。结论围产期PFOS暴露可严重影响新生幼鼠的生长发育,其机制可能与孕鼠GC水平的升高,而导致胎盘及胎儿IGF-1的表达水平降低有关。

Objective To study of the effect and mechanism of perinatal exposure to perfluorooctane sulfonate(PFOS)on growth and development of newborn pups.Methods Sixty specific pathogen free(SPF)SD rats were selected,including 20 male rats and 40 female rats,weighing(200±20)g,provided by Nanjing Qinglongshan animal breeding farm.After 1 week of adaptive feeding,20 pregnant mice were divided into control group and PFOS group according to the random number table method,with 10 mice in each group.The PFOS group was intragastric administration with 1.5 mg·kg^(-1)·d^(-1) PFOS solution,the control group was intragastric administration with isovolumetric 0.05%Tween-20 solution,until 21 st day after birth.The changes of body weights of newborn pups were monitored^(-1) the contents of PFOS in serum and liver were detected by HPLC-MS at 0 th day and 21 st day;all newborn pups were sacrificed at 12 week-old,the heart,liver,spleen,lung,kidney,brain were obtained and weighed to calculate the organ coefficient;the serum glucocorticoid(GC)of pregnant mice and serum insulin-like growth factor-1(IGF-1)of newborn pups were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with control group,the body weights of PFOS group were lower at lactation,the differences were statistically significant(P<0.05);from weaning to 6 week-old,the body weights of PFOS group were lower,the differences were statistically significant(P<0.05);from 9 week-old,there was no significant difference between two groups(P>0.05).The PFOS in serum and liver of PFOS group at 0 th day and 21 st day were high expression,as compared with 0 th day,the expression level of PFOS at 21 st day were higher,the differences were statistically significant(P<0.05).Compared with control group,the heart’s weight and coefficient of PFOS group were lower,while the liver’s weight and coefficient were higher(P<0.05).Compared with the control group,the serum GC level of pregnant mice in the PFOS group was significantly increased,while the expression level of IGF-1 was significantly reduced,and the differences were statistically significant(P<0.05).Conclusion Perinatal exposure to PFOS seriously affect the growth and development of newborn pups,which was probably related with the increase of expression level of GC of pregnant mice and decrease of IGF-1 of newborn pups.