论文部分内容阅读
目的探讨邻苯二甲酸二丁酯(DBP)对大鼠睾丸的损害作用及与细胞外调节蛋白激酶(ERK)信号通路激活、缝隙连接损伤关联性。方法 SD大鼠随机分为3个DBP剂量组(50、500、1 000 mg/kg)和溶剂对照组,经口灌胃染毒,每日1次,持续5周。酶联免疫吸附试验检测大鼠血清卵泡刺激素(FSH)、黄体生成素(LH)、睾酮等生殖激素水平;精子分析仪分析精子密度、活率和总畸形率;苏木素-伊红染色法观察睾丸组织结构变化;Western blot法检测ERK1/2和p-ERK蛋白表达;RT-PCR法检测缝隙连接蛋白43(Cx43)mRNA表达。结果与对照组比较,中、高剂量DBP组大鼠血清睾酮水平[(6.65±0.97)、(3.57±0.54)nmol/L]明显降低(P<0.05),高剂量DBP组大鼠精子密度(64.71±11.36)10~5个/mL显著降低(P<0.05),中、高剂量DBP组大鼠精子总畸形率[(13.64±1.68)%、(19.54±2.86)%]明显升高(P<0.05);随DBP剂量升高大鼠睾丸组织结构损伤程度增加;与对照组比较,中、高剂量DBP组大鼠睾丸组织中p-ERK表达明显升高,各剂量DBP组大鼠睾丸组织中Cx43 mRNA表达均明显下降,差异具有统计学意义(P<0.05)。结论 DBP可激活ERK通路、下调Cx43表达,引起大鼠睾丸组织结构和功能损伤。
Objective To investigate the effects of dibutyl phthalate (DBP) on rat testes and their association with activation of extracellular regulated protein kinase (ERK) signaling pathway and gap junctions. Methods SD rats were randomly divided into 3 DBP dose groups (50, 500 and 1 000 mg / kg) and solvent control groups. The rats were orally administered orally once daily for 5 weeks. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and other reproductive hormones were detected by enzyme linked immunosorbent assay (ELISA); spermatozoa density, viability and total deformity were analyzed by sperm analyzer; hematoxylin and eosin staining The changes of testis tissue structure were observed by immunohistochemistry. The protein expressions of ERK1 / 2 and p-ERK were detected by Western blot and the mRNA expression of connexin43 (Cx43) by RT-PCR. Results Compared with the control group, the levels of serum testosterone in the DBP group were significantly lower than those in the DBP group [(6.65 ± 0.97), (3.57 ± 0.54) nmol / L] (P <0.05) 64.71 ± 11.36) (P <0.05). The total deformity rate of rats in medium and high dose DBP group was significantly higher than that of control group ([(13.64 ± 1.68)% vs (19.54 ± 2.86)% vs <0.05). Compared with the control group, the expression of p-ERK in testis tissue of DBP group was significantly increased with the increase of DBP dose. Compared with the control group, the expression of p- Cx43 mRNA expression were significantly decreased, the difference was statistically significant (P <0.05). Conclusion DBP can activate ERK pathway, down-regulate the expression of Cx43, and cause damage to the structure and function of testis in rats.