摘要
[目的]研究雷公藤红素对3T3细胞的毒性作用,获得的细胞毒性结果预测急性毒性半数致死量（LD50）,并与采用小鼠上下法（UDP）和Bliss法测定的急性毒性数值进行比较。[方法]以已验证的3T3细胞中性红摄取为细胞毒性模型,以0.01-2.05 mg/L的8个浓度（剂间比为2.15）的雷公藤红素进行处理,分别于处理后48 h进行中性红摄取试验,计算半数抑制浓度（IC50）。以RC数学模型预测其全身急性毒性LD50。参考此LD50值设定起始剂量进行小鼠上下法实验。取70只ICR小鼠,雌雄各半,以3、4、5、6、7、8 mg/kg的雷公藤红素溶液和0 mg/kg[4%二甲亚砜（DMSO）氯化钠注射液]静脉给药,观察14 d,根据动物死亡率采用Bliss法计算LD50。[结果]雷公藤红素3T3细胞中性红摄取试验的IC50值为（0.119 7±0.018 7）mg/L（n=2）,决定系数R2〉0.96,预测其全身急性毒性LD50为5.375 mg/kg。上下法起始剂量设为3.3 mg/kg,测得雷公藤红素在ICR小鼠的LD50值为3.157 mg/kg,95%可信区间为3.1-5.5 mg/kg。小鼠Bliss法测定急性毒性LD50为4.899 mg/kg,95%可信区间为4.483-5.354 mg/kg。[结论]雷公藤红素的体外3T3细胞毒性预测急性毒性与体内方法所得数值一致。
[ Objective ] To evaluate the cytotoxicity of celastrol on 3T3 ceils, predict acute toxicity （LDs0） based on the cytotoxicity data, and compare acute toxicity results by using mouse up-and-do0wn method and Bliss method. [ Methods ] In this study, we employed an in-house validated in vitro cytotoxicity model based on the 3T3 ceils neutral red uptake （NRU） assay. Using eight concentrations of celastrol （0.01-2.05 rag/L） for 48 h incubation, we calculated ICso values for celastrol. The LDs0 value of celastrol for systemic toxicity was computed by using RC model to set the starting dose for up-and-down procedure. Seventy ICR mice were divided into seven groups, half male and half female, and administered with 3, 4, 5, 6, 7, 8, and 0mg/kg [40% dimethyl sulfoxide （DMSO） and sodium chloride] of celastrol intravenously. After observation for 14 days, we obtained LDs0 values for celastrol using Bliss method based on the mortality rate. [ Results ] The ICso values for celastrol using 3T3 cells NRU assay was （0.1197 ~ 0.0187） mg/L （n=2）, with coefficient of determination R2 〉 0.96. The computed LDso value for celastrol systemic toxicity was 5.375 mg/kg. The starting dose of up-and-down procedure was 3.3 mg/kg, and the derived LDs0 value was 3.157 mg/kg with 95% confidence interval of 3.1-5.5 mg/kg. The LDso value derived from Bliss method was 4.899mg/kg with 95% confidence interval of 4.483-5.354mg/kg. [ Conclusion ] The acute toxicity of celastrol nredictod by 3T3 cvtotoxicitv test is consistent with the results by in vivo uv-and-down nrocedure and Bliss method.
出处
《环境与职业医学》
CAS
CSCD
北大核心
2015年第6期535-538,548,共5页
Journal of Environmental and Occupational Medicine
基金
上海市教委预算内科研项目(编号:2012JW24)
