摘要
目的研究锰对雄性小鼠睾丸Nrf2信号通路的影响,探索锰致雄性生殖障碍的机制。方法将48只雄性昆明小鼠随机分为对照组、高锰组、高锰+叔丁基对苯二酚(t BHQ)干预组和高锰+异烟肼(INH)干预组。对照组、高锰组皮下注射生理盐水,t BHQ干预组皮下注射50 mg/kg t BHQ,INH干预组皮下注射100 mg/kg INH。2 h后对照组腹腔注射生理盐水,其余三组腹腔注射50 mg/kg Mn Cl2。注射容量均5 ml/kg,持续4周。HE染色观察小鼠睾丸组织形态改变;Western blotting测定睾丸组织内Nrf2、SOD2及GPx-1的蛋白表达水平。结果与对照组比较,高锰组小鼠睾丸组织形态出现损伤;与高锰组比较,t BHQ干预组小鼠睾丸组织形态损伤出现恢复;INH干预组损伤加剧。与对照组比较,高锰组睾丸组织内Nrf2、SOD2及GPx-1的蛋白水平分别下降49.14%、49.42%、39.06%;与高锰组比较,t BHQ干预使上述指标恢复,Nrf2、SOD2及GPx-1分别升高35.77%、31.77%、41.52%;INH干预使之加剧,Nrf2、SOD2及GPx-1分别下降32.71%、14.65%、40.31%。结论锰暴露可通过干扰Nrf2信号通路,造成睾丸组织病理损伤,产生生殖毒性。
To study the effect of manganese on Nrf2 signaling pathway in male mice testis, thereby explore the mechanism of manganese-induced male reproductive disorder. Methods Forty-eight male Kunming mice were randomly divided into control group, high Mn group, Mn plus tert-butylhydroquinone （tBHQ） group and Mn plus isoniazid （INH） group. Control group, high Mn group received subcutaneous injection of physiological saline, tBHQ group received subcutaneous injection of tBHQ （50mg/kg） and INH group received subcutaneous injection of INH （100mg/kg）; two hours later, the controls were injected with normal saline intraperitoneally, the rest groups were intraperitoneally injected with 50 mg/kg of MnCl2 q.o.d, all the injection volume were 5 ml/kg, the Mn administration lasted for four weeks. Then, take the samples of testis and epididymis, HE staining was used to observe the morphological changes of mice testis, and western blotting technique was used to detect the protein expression levels of Nrf2, SOD2 and GPx-1 in the testicular tissue. Results The results shows that compared with control group, there was some morphological damage in the epididymis of Mn-exposed mice; and compared with high Mn group, the morphological damage of testis had some recovered in tBHQ treated mice, but the injury even showed some deterioration in INH treated mice. Additionally, compared with the controls, the protein levels of Nrf2、SOD2 and GPx-1 in the testis of the Mn exposed mice had decreased by 49.14%, 49.42% and 39.06%, respectively; while compared with high Mn group, the indices mentioned above in tBHQ treated mice were increased by 55.70%, 46.55% and 70.98%, respectively, but these indices were all decreased by 32.71%, 14.65% and 40.31%, respectively in INH treated mice. Conclusion The results suggested that manganese exposure could induce pathological damage of testis by interfereing with Nrf2 signaling pathway, thereby resulting in the reproductive toxicity.
作者
史鹏程
吴凤迪
杨欣欣
杨海波
徐斌
刘巍
邓宇
SHI Peng-cheng;WU Feng-di;YANG Xin-xin;Yang Hai-bo;XU Bin;LIU Wei;DENG Yu(Department of Environmental Health, School of Public Health, China Medical University, Shenyang110122,China)
出处
《中国工业医学杂志》
CAS
2018年第3期163-167,F0003,共6页
Chinese Journal of Industrial Medicine
基金
国家自然科学基金项目(编号:81302406)
