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目的探讨亚硝酸盐暴露对雄性小鼠生殖毒性的分子机制。方法 36只2月龄健康雄性小鼠,随机分为对照组(生理盐水)、低剂量组(60 mg/kg)和高剂量组(120 mg/kg),每组12只进行亚硝酸盐灌胃3个月,观察小鼠的生长状况,HE染色法观察睾丸组织病理变化,免疫荧光和Western blotting方法分析检测睾丸组织细胞增殖与凋亡情况及DNA甲基化、组蛋白去乙酰化相关酶的表达情况。结果亚硝酸盐暴露组小鼠较对照组小鼠体重增加缓慢,睾丸指数降低(P<0.01),形态发生病理性改变;亚硝酸盐暴露组小鼠睾丸组织细胞增殖较对照组明显减少,细胞凋亡较对照组明显增加(P<0.01);同时DNA甲基化和组蛋白去乙酰化水平高于对照组(P<0.01),且均具有剂量依赖性。结论亚硝酸盐暴露通过抑制雄性小鼠生长发育及睾丸生精细胞增殖,诱导睾丸生精细胞凋亡,造成雄性生殖毒性;DNA甲基化及组蛋白去乙酰化水平升高,提示表观遗传学可能参与了亚硝酸盐暴露对雄性生殖系统的损伤过程及调控机制。
Objective To explore the molecular mechanism of reproductive toxicity of nitrite exposure in male mice. Methods Thirty - six healthy 2 - month - old male mice were randomly divided into control group (saline), low dose group (60 mg / kg) and high dose group (120 mg / kg) Stomach for 3 months, the growth of mice was observed, the histopathological changes of testis were observed by HE staining, the proliferation and apoptosis of testicular cells and the expression of DNA methylation, histone deacetylase related enzymes The expression of the situation. Results Compared with the control group, the body weight of mice exposed to nitrite increased slowly and the index of testis decreased (P <0.01). Pathological changes were observed in the mice exposed to nitrite exposure. The proliferation of mouse testis tissue in nitrite exposure group was significantly decreased compared with the control group. Apoptosis was significantly increased compared with the control group (P <0.01). DNA methylation and histone deacetylase levels were significantly higher than those in the control group (P <0.01), and both of them were dose-dependent. Conclusion Nitrite exposure induces apoptosis of spermatogenic cells in testis by inhibiting the growth and development of male mice and inducing male reproductive toxicity. DNA methylation and histone deacetylation levels are elevated, suggesting that epigenetic Learning may be involved in the nitrite exposure of the male reproductive system damage process and regulatory mechanisms.