纳米二氧化硅经鼻黏膜染毒对大鼠睾丸毒性的机制研究

目的：利用蛋白质组学技术研究纳米二氧化硅颗粒对SD雄性大鼠生殖系统的损伤机制，为深入了解纳米材料的毒性效应及机制提供科学依据。方法：采用鼻腔滴入纳米二氧化硅分散液方式对SD雄性大鼠进行染毒，设置为纳米二氧化硅组；同时经鼻腔滴入生理盐水设置为生理盐水对照组。两组于4周后断颈处死并取睾丸组织。利用荧光差异双向电泳（2D-DIGE）联合基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）技术筛选并鉴定出差异表达蛋白，Western blot验证差异蛋白。结果：共筛选并鉴定出9个差异表达的蛋白，分别是GRP78、HSP7C、KNT1、HSP72、ALBU、STIP1、PDIA1、ALDR和GDIR1；并经Western blot验证了PDIA1和HSC70表达水平变化与2D-DIGE实验结果一致。结论：本研究发现纳米二氧化硅作用后大鼠睾丸组织中凋亡相关蛋白PDIA1和HSC70发生异常变化，初步阐明了二氧化硅染毒导致大鼠生殖毒性的细胞凋亡分子机制，为预防纳米二氧化硅毒性奠定基础。

Mechanisms for induction of reproductive toxicity by nano-SiO particles2in SD male rats

OBJECTIVE:To study the adverse effect of nano-SiO particles on reproductive system in male SD2 rats. METHODS:Male rats were treated with nano-SiO particles or saline and then executed 4 weeks later. Testes were2 isolated for the extraction of protein. 2D-DIGE coupled with MALDI-TOF-MS was used to identify nano-SiO induced2 abnormal expression of proteins. Two proteins were verified by Western blot analysis. RESULTS:Nano-SiO induced2 abnormal expression of 9 proteins in rat testes (GRP78,HSP7C,KNT1,HSP72,ALBU,STIP1,PDIA1,ALDR and GDIR1). PDIA1 and HSP7C were validated by Western blot analysis,and the results were accordance with DIGE analysis. CONCLUSION:Our findings partially supported our early observation regarding seminiferous tubule dysgenesis in rat. In addition,this study revealed technological advancement in reproductive toxicology of SiO2 .