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[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] The study aimed to study the toxicity of tripterine on 3T3 cells and the obtained cytotoxicity results to predict the LD50, which was compared with the acute toxicity values determined by the mouse upper and lower methods (UDP) and Bliss method . [Method] The 3T3 cells were verified to be cytotoxic by neutral red uptake and treated with triptolide at the concentration of 0.01 ~ 2.05 mg / L (dose - to - time ratio was 2.15). After treatment for 48 h Neutral red uptake test was performed to calculate the half maximal inhibitory concentration (IC50). Predicting acute systemic toxicity LD50 by RC mathematical model. Set the initial dose with reference to the LD50 value to perform the mouse experiment. Seventy ICR mice, male and female, were treated with tripterine at 3,4,5,6,7,8 mg / kg and 0 mg / kg [4% dimethylsulfoxide (DMSO) Injection] intravenous administration, observed 14 d, according to animal mortality rate calculated by the Bliss LD50. [Results] The IC50 value of triptolide 3T3 cells in neutral red uptake test was (0.119 7 ± 0.018 7) mg / L (n = 2), and the coefficient of determination R2> 0.96. The acute systemic toxicity LD50 was 5.375 mg / kg. Upper and lower initial dose was set at 3.3 mg / kg, measured triplotidine in ICR mice LD50 value was 3.157 mg / kg, 95% confidence interval of 3.1 to 5.5 mg / kg. The acute toxicity LD50 of mouse Bliss method was 4.899 mg / kg, 95% confidence interval was 4.483 ~ 5.354 mg / kg. [Conclusion] The acute toxicity of tripterine on in vitro cytotoxicity of 3T3 is consistent with that obtained from in vivo methods.