| 摘 要: 目的 探讨磷酸锰铁锂(LiMnFePO4)可否通过Keap1/Nrf2信号通路影响雄性小鼠的生殖系统。方法 将18只8周龄C57BL/6J小鼠随机分为对照组和低、高剂量(5、50mg/kg)LiMnFePO4组,每组6只,灌胃染毒6周处死。取出睾丸,称取小鼠体质量并计算睾丸和附睾脏器系数、精子计数和精子畸形率,检测小鼠睾丸组织丙二醛(MDA)、超氧化物歧化酶(SOD)活性水平,观察睾丸组织形态,测定小鼠睾丸组织Kelch样环氧氯丙烷相关蛋白-1(Keap1)和核因子红细胞2相关因子2(Nrf2)、血红素氧合酶1(HO-1)的蛋白和mRNA表达水平。结果 LiMnFePO4暴露对小鼠体质量、睾丸和附睾脏器系数影响差异无统计学意义;LiMnFePO4染毒小鼠睾丸组织SOD活性水平降低,MDA水平升高;小鼠睾丸组织Keap1的蛋白和mRNA表达水平升高,HO-1的蛋白和mRNA表达水平降低,Nrf2的蛋白表达水平降低、mRNA表达水平升高;高剂量LiMnFePO4染毒小鼠睾丸组织精子计数减少,精子畸形率上升,睾丸曲细精管皱缩,管内精细胞减少、排列混乱,睾丸间质细胞增生。结论 LiMnFePO4可能通过Keap1/Nrf2信号通路影响小鼠睾丸组织氧化应激状况,导致雄性小鼠生殖毒性。 |
| 关键词: 磷酸锰铁锂(LiMnFePO4 ) 生殖毒性 Kelch样环氧氯丙烷相关蛋白-1(Keap1) 核因子红细胞2相关因子2(Nrf2) |
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中图分类号: R994.6
文献标识码: A
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| 基金项目: 徐州市青年科技人才项目(编号:KC23028);徐州医科大学优秀人才启动基金(编号:D2020019);江苏省高等学校大学生创新创业训练计划项目(编号:202210313122Y) |
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| Lithium manganese iron phosphate affects reproductive system of male mice via Keap1 / Nrf 2 signaling pathway |
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PAN Linwei,QI Zhipeng,YANG Haibo,ZOU Cheng,YAN Jikuan,SONG Weiyi,LI Wei,YANG Xinxin
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School of Public Health,Xuzhou Medical University,Xuzhou,Jiangsu 221004,China
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| Abstract: Objective To explore whether the exposure of lithium manganese iron phosphate(LiMnFePO4 )can affect the reproductive system of male mice through the Keap1/Nrf2 signaling pathway.Methods Eighteen C57BL/6J mice(8-week-old)were randomly divided into control group,low dose(5mg/kg)LiMnFePO4 group and high dose(50mg/kg)LiMnFePO4 group,six mice each group; which were given LiMnFePO4 by daily gavage for six weeks. Then, the mice were killed and remove the testicles, weight the body weights of mice,calculate the coefficients of testicular and epididymal organs,sperm count and sperm malformity rate,detect the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)activity in testicular tissue,observe the morphology of testicular tissue and measure the protein and mRNA expression levels of Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid-2 related factor 2(Nrf 2) and heme oxygenase-1(HO-1) in mice testicular tissues. Results The results showed that the exposure of LiMnFePO4 didnt have significant effect on body weight and testicular organ coefficient and epididymal organ coefficient of mice, but the SOD activity in testicular tissue of LiMnFePO4 exposed mice decreased and the MDA level increased;meanwhile,the protein and mRNA levels of Keap1 in mice testicular tissues increased as well as the expression level of Nrf2 mRNA, and the levels of protein and mRNA of HO-1,as well as protein of Nrf2 were decreased.Furthermore,it was found that there a decrease in sperm count and an increase in sperm malformity rate in testicular tissue of mice,the seminiferous tubules of testes were wrinkled,the number sperm cells in the tubules were reduced and chaotic arrangement,the interstitial cells of testes exhibit proliferation.Conclusion The results suggested that LiMnFePO4 may affect the oxidative stress in mice testicular tissues through Keap1/Nrf2 signaling pathway, then leads to reproductive toxicity in male mice. |
| Keywords: lithium manganese iron phosphate(LiMnFePO4) reproductive toxicity Kelch-like ECH-associated protein 1(Keap1) nuclear factor erythroid-2 related factor 2(Nrf2) |
