纳米氧化铜对小鼠遗传毒性及氧化应激的研究

Study of genetoxicity and oxidative stress induced by copper oxide nanoparticles in mice

目的 研究纳米氧化铜对小鼠的遗传毒性及氧化应激水平.方法 30只小鼠随机分成对照组、50、150 mg/kg纳米氯化铜染毒组,染毒组分别一次性腹腔注射50、150 mg/kg纳米氧化铜,对照组给予含0.05％ Tween 80相同体积的生理盐水.于染毒前及染毒后24、48及72 h分别测定尾静脉外周血网织红细胞微核发生率和尿中8-羟基-脱氧鸟嘌呤核苷（8-OH-dG）水平.染毒72 h,处死小鼠,取肝、肾和股骨骨髓,分别提取DNA并测定DNA中8-OH-dG.结果 50 mg/kg染毒组48 h,150 mg/kg组24和48 h外周血网织红细胞微核发生率（3.1 1‰±1.46、4.25‰±0.43‰、5.42‰±0.76‰）比两组染毒前（1.55‰±0.39‰、1.11‰±0.19‰）及相应的对照组（1.55‰±0.28‰、1.00±0.67‰）明显升高,差异有统计学意义（P＜0.05或P＜0.01）.与染毒前及对照组比较,各时间50、150 mg/kg染毒组尿8-OH-dG水平（ng/mg尿肌酐）均明显升高,差异有统计学意义（P＜0.05或P＜0.01）.50和150 mg/kg组肝组织DNA中8-OH-dG水平（4.53±1.27、7.69±2.78）明显高于对照组（0.85±0.14）,差异有统计学意义（P＜0.01）.结论 纳米氧化铜对小鼠具有遗传毒性,并致其氧化应激水平升高.

Objective To investigate the genotoxicity and oxidative stress induced by copper oxide nanoparticles in mice.Methods Thirty mice were randomly divided into control group and low-and high-dose exposure groups.The low-and high-dose exposure groups were given copper oxide nanoparticles （50 and 150 mg/kg） by a single intraperitoneal injection,while the control group was given an equal volume of normal saline containing 0.05％ Tween 80.The micronucleus rate of reticulocytes in peripheral blood from the caudal vein and urinary 8-hydroxy-deoxyguanosine （8-OH-dG） level were measured before and at 24,48,and 72 h after exposure.All the mice were sacrificed at 72 h after exposure,the liver,kidney,and femoral marrow were taken for DNA extraction,and 8-OH-dG in DNA was quantified.Results The micronucleus rates of peripheral blood reticulocytes in low-dose exposure group at 48 h （3.11±1.46‰） and in high-dose exposure group at 24 and 48 h （4.25±0.43‰ and 5.42±0.76‰） were significantly increased compared with those before exposure （1.55±0.3‰and 1.11±0.19‰） and those in control group （1.55±0.28‰ and 1.00±0.67‰） （P＜0.05 or P＜0.01）.The urinary 8-OH-dG levels （ng/mg creatinine） in low-and high-dose exposure groups at all time points were significantly increased compared with those before exposure and those in control group （P＜0.05 or P＜0.01）.The low-and high-dose exposure groups had significantly higher content of 8-OH-dG in liver DNA than the control group （4.53±1.27 and 7.69±2.78 vs 0.85±0.14,P＜0.01）.Conclusion Copper oxide nanoparticles cause genotoxicity and increase oxidative stress in mice.