纳米银凝胶在家兔体内的生殖器官毒性及体外细胞毒性研究

目的: 为了明确纳米银凝胶的体内生殖器官毒性和体外细胞毒性。 方法: 通过检测和观察生殖器官内银的蓄积、组织病理学及超微病理的变化,对纳米银凝胶在家兔体内生殖器官的吸收、蓄积和组织细胞的病理变化以及体外细胞毒性进行了系统研究。 结果: 研究结果显示兔子阴道内连续给药6 d后生殖器官内银含量均较对照组显著增加,在生殖器官组织内造成不同程度的纳米银蓄积,引起了阴道粘膜组织和子宫内膜组织,乃至卵巢组织不同程度的超微病理变化,诸如线粒体肿胀、内质网扩张及空泡形成等。体外细胞试验同样显示了纳米银凝胶暴露后,纳米银在细胞内的蓄积、细胞内大量的空泡形成及微核现象。 结论: 这些结果提示纳米银凝胶持续大量应用会产生一定的毒性反应。子宫内膜及卵巢组织内许多凋亡细胞的存在,提示纳米银凝胶可能存在遗传毒性及生殖毒性风险。结合既往研究的DNA微阵列分析,ROS相关的金属结合蛋白家族基因的显著增高,JAK-STAT信号通路的激活可能是纳米银凝胶引起生殖器官组织超微病理变化的主要作用机制。

Objective: To well understand the in vivo toxicity in reproductive organs and in vitro cytotoxicity of silver nanoparticle based-hydrogel. Methods: Inductively coupled plasma-mass spectrometer (ICP-MS),histopathological observation and transmission electron microscopy (TEM) were used for the investigation of uptaken and accumulation of Ag-NPs in reproductive organs,and micro-pathological changes of the tissues, as well as in vitro cytotoxicity after Ag-NPs/Gel exposure. Results: The findings showed that the silver-NPs content in some reproductive organs was increased to compare that in the control group after 6 days continuously exposure of Ag-NPs/Gel in the rabbit vagina,and micro-pathological changes in reproductive organs were observed,like mitochondria swelling,endoplasmic reticulum expansion and vacuole,etc.The Ag-NPs/Gel exposure to HeLa cells also showed the accumulation of Ag-NPs and vacuole,micronuclei formation in the cells. Conclusion: These results suggest that the continuously use of Ag-NP/Gel possibly to cause micro-pathological level changes in the reproductive organs,may be increase the reproductive toxicity risk.Taken together with our previous study,the up-regulation of metallothionein genes,which related to ROS signal pathway,NF-kappaB and JAK-STAT signal pathway-related genes may be the important mechanisms of the Ag-NPs/Gel exposure-induced micro-pathological changes in reproductive organ tissues.