二氧化钛纳米材料对氧化应激状态大鼠肾脏的毒性

Toxicity of nano-TiO_2 in rat kidney under oxidative stress

目的研究二氧化钛(TiO2)纳米材料对正常及氧化应激SD大鼠肾组织的不良影响。方法通过肌肉注射四氧嘧啶,构建氧化应激模型,并分为四氧嘧啶处理组(OS组)、纳米TiO2处理组(NM组)及四氧嘧啶与纳米TiO2共处理组(OS-NM组),后两组分别采用一次性腹腔注射0.5、5和50mg/kg体质量纳米TiO2的方式进行染毒,另设正常对照组。检测氧化应激指标、尿素氮(BUN)水平并制备肾组织病理切片。结果注射5mg/kg体质量纳米TiO2时,OS-NM组大鼠O2-·和超氧化物歧化酶(SOD)较OS组和NM组增高,差异均有统计学意义(P<0.05);当注射50mg/kg体质量纳米TiO2时,与OS组及NM组分别比较,OS-NM组大鼠的O2-·、谷胱甘肽(GSH)和SOD水平变化差异均极显著(P<0.01);且OS组与NM组相比较,O2-·和GSH的变化有统计学意义(P<0.05)。与染毒后的正常大鼠相比,纳米TiO2导致氧化应激大鼠BUN水平的异常升高(P<0.01),并引起肾脏出现肾小球体积增大、细胞数目增多、肾小管上皮细胞水肿。方差分析表明四氧嘧啶与纳米TiO2在导致O2-·水平升高的过程中存在协同作用。结论 TiO2纳米材料对正常及氧化应激大鼠肾脏均有损伤,且四氧嘧啶与纳米TiO2协同作用能诱发更为严重的氧化应激状态从而加重对肾脏的损伤,这为患者安全使用纳米材料提供了一定的实验依据。

Objective To investigate the adverse effects of nano-titanium dioxide （TiO2 ）on kidney tissues in healthy rats and rats with oxidative stress （OS）.Methods Thirty-six healthy male SD rats were randomly divided into control group, alloxan-treated group, nano-TiO2 treated （NM） group, and alloxan and nano-TiO2 dual treatment （OS-NM）group.Nano-TiO2 of three concentrations （0.5,5 and 50 mg/kg body weight）was injected intraperitoneally.The level of OS biochemical factors and blood urea nitrogen （BUN）and pathological changes of kidney were determined.Results Compared with those in NM and OS groups,the levels of O2 -· and superoxide dismutase （SOD）in OS-NM group were significantly increased after exposure to nano-TiO2 of 5 mg/kg body weight （P 〈0.05）.Nano-TiO2 of 50 mg/kg body weight led to significant changes of O2 -·,SOD,and glutathione （GSH） levels in OS-NM group in comparison with OS and NM groups （P 〈0.01）.The levels of O2 -· and GSH between OS group and NM group changed significantly （P 〈 0.05 ）.Compared with healthy rats,OS rats showed significant increased BUN level （P 〈0.01）,cell number and edema of renal tubular epithelial cells after nano-TiO2 exposure.A synergic effect between OS condition and nano-TiO2 level was shown on the increased level of O2 -·.Conclusion Nano-TiO2 induced more adverse effects on the kidney in OS rats,suggesting a synergistic effect between nano-TiO2 and OS.This result provides experimental evidence for patients’safe use of nano-TiO2 .