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目的研究c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)在邻苯二甲酸二(2-乙基)己酯[di(-2-ethyl-hexyl)phthalate,DEHP]诱导的尿道下裂大鼠阴茎组织中的表达变化,探讨尿道下裂发生的机制。方法将孕12 d(gestation day,GD12)的SD孕鼠随机分为2组:实验组[将DEHP溶于1.5 ml大豆油中灌胃大鼠,750 mg/(kg.d)]和对照组(以1.5 ml大豆油灌胃大鼠),每组20只,自GD12～GD19连续每天定时给药1次。各组分别取10只孕鼠正常分娩,雄性仔鼠出生后30 d,计数每窝产雄性活仔数,称量体重,并测量肛门生殖器距离(anogenital distance,AGD),逐个检查雄鼠的阴茎弯曲度和尿道开口部位,判断有无尿道下裂;其余孕鼠在怀孕第20天行剖宫产取出胎鼠,采用实时定量PCR(qPCR)和免疫组化法分别检测雄性胎鼠阴茎组织中JNK1和JNK2 mRNA和蛋白的表达水平。结果雄性仔鼠出生后30 d,实验组与对照组比较,每窝产雄性活仔数、雄性仔鼠的体重及AGD均有明显减少或缩短(P均<0.001);实验组尿道下裂发生率约为30.6%。与对照组比较,实验组胎鼠阴茎组织中JNK1和JNK2mRNA的水平明显增加(P<0.05),磷酸化JNK1和JNK2蛋白的表达水平有增加的趋势。结论 DEHP诱导的先天性尿道下裂可能与胎鼠阴茎组织中JNK通路异常表达有关。
Objective To investigate the effects of c-Jun N-terminal kinase (JNK) on the urethra induced by di (2-ethyl-hexyl) phthalate (DEHP) The change of expression in the penile tissue of rat undergoing hypothyroidism to explore the mechanism of hypospadias. Methods Pregnant SD pregnant rats of gestation day (GD12) were randomly divided into two groups: experimental group [DEHP dissolved in 1.5 ml of soybean oil and fed into the stomach of rats, 750 mg / (kg · d)] and control group (1.5 ml of soybean oil fed rats), each group of 20, from GD12 ~ GD19 continuous daily administration of 1 time. Ten pregnant rats in each group were given normal delivery. Male offspring were born 30 days after birth, and the number of male alive pups was counted in each litter. Body weight was measured and the anogenital distance (AGD) was measured. The male penis Flexion and urethral opening to determine whether there is hypospadias; the other pregnant rats were removed by cesarean section on the 20th day of pregnancy fetus, using real-time quantitative PCR (qPCR) and immunohistochemistry were detected in male penile tissue JNK1 and JNK2 mRNA and protein expression levels. Results Compared with the control group, male offspring live birth weight per litter and AGD of male offspring were significantly reduced or shortened (P <0.001) 30 days after birth in male offspring. Compared with the control group, the experimental group had hypospadias The rate is about 30.6%. Compared with the control group, the levels of JNK1 and JNK2 mRNA in the penile tissue of the experimental group were significantly increased (P <0.05), while the expressions of JNK1 and JNK2 protein increased. Conclusions DEHP-induced congenital hypospadias may be related to abnormal expression of JNK pathway in fetal rat penile tissue.