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[目的]应用定量构效关系研究方法分别构建两个可用于预测金属氧化物纳米材料对人正常肝细胞(L02细胞)和人肝癌细胞(Hep G2细胞)毒性的预测模型。[方法]在16种金属氧化物纳米材料中,随机选取12种纳入测试集用于模型构建,另4种纳入验证集用于模型验证,尝试在所研究金属氧化物纳米材料的结构参数和其对L02细胞及Hep G2细胞半数抑制浓度(IC50)间分别构建出两个具有统计学意义的纳米定量构效关系模型。[结果]成功地运用一个结构参数核核排斥能构建了一个可用于预测金属氧化物纳米材料对L02细胞毒性的预测模型lg IC50=-0.000 056 2ECORE+3.34(拟合统计量:n=12,F=35.38,R2=0.72,P<0.005);用传导能以及最高轨道能和最低轨道能总和的二分之一构建了一个能够用来预测金属氧化物纳米材料对Hep G2细胞毒性的预测模型lg IC50=-0.1EEc+0.307EShift+3.67(拟合统计量:n=12,F=10.53,R2=0.70,P<0.005)。[结论]本次构建的两个模型R2均大于0.6,符合模型构建要求,对金属氧化物纳米材料的设计和安全性评价具有一定的参考价值。
[Objective] The purpose of this study was to establish two predictive models that could be used to predict the toxicity of metal oxide nanomaterials to human normal hepatocytes (L02 cells) and human hepatocellular carcinoma cells (Hep G2 cells) using quantitative structure-activity relationship studies. [Method] Among 16 kinds of metal oxide nanomaterials, 12 kinds of inclusion test sets were randomly selected for model building and the other 4 kinds of verification sets were used for model verification. Attempts were made to study the structural parameters of metal oxide nanomaterials Two statistically significant QSAR models were constructed for L02 cells and Hep G2 cell half-inhibitory concentration (IC50), respectively. [Results] A predictive model that could be used to predict the cytotoxicity of metal oxide nanomaterials on L02 cells was constructed successfully using one of the structural parameters of nuclear exclusion. Lg IC50 = -0.000 056 2ECORE + 3.34 (Fitting statistics: n = 12, F = 35.38, R2 = 0.72, P <0.005). A predictive model that can be used to predict the cytotoxicity of metal oxide nanomaterials on Hep G2 cells was constructed using the conduction energy and one-half of the sum of the highest orbital energies lg IC50 = -0.1EEc + 0.307EShift + 3.67 (fitted statistics: n = 12, F = 10.53, R2 = 0.70, P <0.005). [Conclusion] The R2 of the two models constructed in this study are both greater than 0.6, which is in line with the requirements of model construction and has some reference value for the design and safety evaluation of metal oxide nanomaterials.