基于cAMP信号通路使用双酚A调节miRNA成熟对青春期鼠雄性生殖系统的影响

Effects of bisphenol A on male reproductive system of adolescent rats by regulating miRNA maturation based on cAMP signaling pathway

目的 探讨通过cAMP信号通路使用双酚A(BPA)调节miRNA成熟对青春期鼠雄性生殖系统的影响。方法 选取60只SD健康雄性大鼠,其中15只为正常组,其余45只随机分为低、中、高剂量组,分别使用5、50、500 mg/kg双酚A进行干预。RT-PCR法检测miR-22、miR-152表达,计算大鼠双酚A对睾丸脏器系数和精子畸形率的影响,检测各组大鼠生殖系统重量、体质量,检测LDH、G6PD活性,Western blot法检测cAMP通路蛋白表达。结果 高剂量组大鼠miR-22表达(0.89±0.10)低于其他组,miRiR-152表达(2.01±0.26)高于其他组,差异均有统计学意义(均P<0.05)。高剂量组大鼠器官系数、体质量下降、精子畸形率均高于其他组,差异均有统计学意义(均P<0.05)。高剂量组大鼠LDH、G6PD活性(0.32±0.0、0.84±0.59)低于其他组,差异均有统计学意义(均P<0.05)。结论 双酚A干预能够调控miR-22、miR-152表达,其作用机制可能与cAMP信号通路受到双酚A有效调控miRNA有关。

Objective To investigate the effects of regulating miRNA maturation through cAMP signaling pathway with bisphenol A(BPA) on male reproductive system of adolescent rats.Methods Sixty SD healthy male rats were selected, of which 15 were normal group, and the other 45 were randomly divided into low-dose, medium-dose and high-dose groups, receiving 5, 50 and 500 mg/kg bisphenol A, respectively. The expression of miR-22 and miR-152 was detected by RT-PCR, and the testicular organ coefficient and sperm malformation rate of rats were calculated. Reproductive system weight and body weight of rats in each group were detected, LDH and G6 PD activities were detected, and the relative expression level of cAMP pathway protein was detected by Western blot.Results The expression of miR-22 in high-dose group(0.89±0.10) was lower than that in other groups, and the expression of miR-152 in high-dose group(2.01±0.26) was higher than that in other groups, with statistical significance(P<0.05).Organ coefficient, body weight decrease and sperm malformation rate of rats in high-dose group were higher than those in other groups, with statistical significance(P<0.05).The activities of LDH and G6 PD in high-dose group(0.32±0.0, 0.84±0.59) were lower than those in other groups, and the differences were statistically significant(P<0.05).Conclusion Bisphenol A intervention can regulate the expression of miR-22 and miR-152, and its mechanism may be related to the effective regulation of miRNA in cAMP signaling pathway by bisphenol A.