纳米银植入大鼠皮下组织亚慢性毒性及在不同组织中的分布

背景:有实验报道纳米银的生物材料直接与人体接触或植入体内,能够产生不良的生物学效应.目的:验证纳米银对人体是否存在潜在的不良生物学反应,评价其生物安全性.设计、时间及地点:动物实验观察,2005-06/2006 06在中国药品生物制品检定所以来器械检测中心完成.材料:纳米银粉和微米银粉为美国Sigma化学试剂公司产品.方法:将大鼠随机分为3组:纳米银组,微米银组,空白对照组,10只/组,雌雄各半.纳米银粉组和微米银粉组皮下植入进行亚慢性毒性试验.实验开始时植入1次,植入剂昔为0.33 g/kg.对照组只做手术,不给药.同时,每组随机选择4只大鼠,对12只大鼠的血清和部分脏器使用等离子体质谱分析仪进行银在大鼠各脏器中分布的测定.主要观察指标:血液生化学指标,脏器系数,银含量.结果:与对照组比较,给药组大鼠的个别脏器系数与对照组比较有显著性差异,但各给药组脏器的绝对质量与对照组比较没有湿著性差异,结合起来分析脏器系数的异常不具有临床意义.其它各脏器系数均在正常值范围内,与对照组比较尤显著性差芹.末见与受试物毒性作用有关的病理组织学改变,给予纳米银粉大鼠末见毒件反应.结论:纳米银对人体可能存在潜在的不良生物学效应.

Nanosilver subchronic toxicity and silver distribution in different rat tissues

BACKGROUND: It has been reported that nanosilver-containing biomaterials produce bad biological effects after they directly contact with or are implanted into human body.OBJECTIVE: To investigate whether nanosilver yields potential adverse biological effects on human body and to evaluate its bioiogical safety.DESIGN, TIME AND SETTING: An animal experiment observation was performed at the Medical Device Center of National Institute for the Control of Pharmaceutical and Biological Products from June 2005 to August 2006.MATERIALS: Nanosilver particles and microsilver particles were purchased from Sigma Company, USA.METHODS: Thirty rats were randomly divided into 3 groups, with 5 male and 5 female rats per group: nanosilver, microsilver, and blank control. Nanosilver and microsilver particles were respectively and subcutaneously implanted for subchronic toxicity test.The nanosilver and microsilver groups were given 0.33 g/kg nanosilver and microsilver, respectively. Rats from the blank control group received identical procedure, with the exception of drug application. Four rats were selected from each group for determination of silver content in serum and some organs by plasma mass spectrometry.MAIN OUTCOME MEASURES: serum biochemical indices, organ coefficient, and silver content.RESULTS: There was significant difference in individual organ coefficient between each drug application group and blank control group. But no significant difference in absolute mass was found between each drug application and the blank control group.These findings suggested no clinical significance of organ coefficient. Other organ coefficients were in the normal range, and there was no significant difference between each drug application group and the blank control group. Patho-histological changes related to toxicity were not found. Rats from the nanosilver group did not show toxic reaction.CONCLUSION: Nanosilver produces potential adverse biological effects after implanted into human body.