恩诺沙星、喹烯酮、土霉素和硫酸多黏菌素B对细胞的联合毒性研究

doi:10.16431/j.cnki.1671-7236.2022.02.031

摘要/Abstract

摘要： 【目的】探讨常见兽药恩诺沙星(ENR)、喹烯酮(QCT)、土霉素(OTC)和硫酸多黏菌素B(PMB)对细胞的单一及联合毒性效应。【方法】以L02、AML12、Marc145、HEK293T、TM3和SK-N-SH细胞为模型, 通过结晶紫染色获得不同浓度下4种药物对6种细胞的相对抑制率, 进行浓度-效应方程拟合, 并分别计算药物在不同生长抑制率下的效应浓度(EC_F, 其中F=10、20、25、33、50)。按EC₅₀∶EC₅₀、EC₃₃∶EC₃₃∶EC₃₃、EC₂₅∶EC₂₅∶EC₂₅∶EC₂₅的比例分别进行二元、三元、四元药物等毒性比混合, 以1/2为稀释因子进行浓度梯度处理, 计算抑制率并拟合实际作用曲线, 采用浓度加和模型(CA)和独立作用模型(IA)法评价不同药物之间的联合效应。【结果】 4种药物对6类细胞的生长抑制均存在剂量-效应关系, 无论在哪种细胞中, QCT的毒性最强, PMB毒性最小。4种抗菌药两两组合出现协同的概率较高, 尤其是与OTC的组合, OTC+QCT在6种细胞中均有明显的协同抑制。TM3细胞中易出现相加而对肝细胞和肾细胞协同的可能性更大, 对不同的细胞同一组合的效应变化可能不同。在三元和四元组合中, 相加效应出现的概率上升且变化更为复杂, 易随浓度的变化出现多段效应。【结论】常见兽药对肝脏、肾脏、神经及生殖细胞具有一定毒性, 且这些药物的联合毒性效应不是简单的相加, 组分、浓度等会影响联合效应, 在应用时要注意配伍禁忌。

关键词: 兽药; 联合作用; 浓度加和模型(CA); 独立作用模型(IA)

Abstract: 【Objective】 The study was aimed to investigate the single and combined toxic effects of enrofloxacin (ENR), quinolone (QCT), oxytetracycline (OTC) and polymyxins B sulfate (PMB) on cells.【Method】 L02, AML12, Marc145, HEK293T, TM3 and SK-N-SH cells were used as models.The inhibition rates of four drugs on six kinds of cells at different concentrations were obtained by crystal violet staining and the concentration-effect equations were fitted.EC_F(the drug concentration at F% inhibition rate (F=10, 20, 25, 33, 50)) was calculated.Binary, ternary and quaternary medicines were mixed respectively at the toxicity ratio of EC₅₀∶EC₅₀, EC₃₃∶EC₃₃∶EC₃₃, EC₂₅∶EC₂₅∶EC₂₅∶EC₂₅ and then diluted with a dilution ratio of 1/2.The inhibition rates were calculated and the actual action curves were fitted.Concentration addition model (CA) and independent action model (IA) were used to evaluate the combined effects of different drugs.【Result】 There was a dose-effect relationship between the four drugs on the growth inhibition of six kinds of cells.QCT showed the strongest toxicity while PMB showed the weakest toxicity.Binary combination showed high probability of synergism, especially the combination with OTC, and OTC+QCT showed significant synergistic inhibition in the six kinds of cells.The joint effects were prone to addition on TM3 while had a greater possibility of synergy on liver and kidney cells, and the same combination might have different effects on different cells.In ternary and quaternary combinations, the probability of additive effect increased, and the change of the combined effect was more complex, which was easy to appear multi-segment effect with the change of concentration.【Conclusion】 Common veterinary drugs had certain toxicity to liver, kidney, nerve and germ cells, and the combined toxic effects of these drugs were not simply additive, which were affected by components, concentration and so on, so incompatibility should be paid attention in the application.

Key words: veterinary medicine; joint effect; concentration addition model (CA); independent action model (IA)

中图分类号:

S859.79⁺6

傅榆涵, 侯力睿, 赵冲, 扈洪波, 尹淑涛. 恩诺沙星、喹烯酮、土霉素和硫酸多黏菌素B对细胞的联合毒性研究[J]. 中国畜牧兽医, 2022, 49(2): 687-699.

FU Yuhan, HOU Lirui, ZHAO Chong, HU Hongbo, YIN Shutao. Study on Joint Toxicity of Enrofloxacin, Quinocetone, Oxytetracycline and Polymyxin B Sulfate to Cells[J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(2): 687-699.

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