The mechanisms of local anesthetics toxicity by discrimination between apoptosis and necrosis

许多研究表明，局麻药具有细胞毒性并可诱导细胞凋亡，但局麻药的种类和诱导细胞凋亡的速率尚不清楚。本研究的目的是阐明诱导细胞凋亡或坏死的局麻药及其诱导相关因素。方法：观察利多卡因、甲比卡因、布比卡因、罗比卡因、丁卡因、地布卡因、普鲁卡因和QX-314对HL-60人白血病细胞株的凋亡和坏死作用。用碘化丙啶(PI)和膜联蛋白-V(Annexin-V)双染色法检测细胞的凋亡和坏死，并用流式细胞仪(FACS)检测细胞的凋亡和坏死情况。结论：脂类活性高的局麻药毒性大，以坏死为主，而PKA低的局麻药可诱导更多的细胞凋亡。

Many studies have indicated that local anesthetics are cytotoxic and can induce apoptosis; however, the types of local anesthetics and the induction rates of apoptosis remain unclear. The aim of this study was to clarify the local anesthetics that induce apoptosis or necrosis and their induction-related factors. Methods : Lidocaine, mepivacaine, bupivacaine, ropivacaine, tetracaine, dibucaine, procaine, and QX-314 were evaluated for apoptosis and necrosis in HL-60 human leukemia cell lines. Apoptosis and necrosis were analyzed by double-staining assay with propidium iodide (PI) and annexin-V and were measured by flow cytometry (FACS). DNA fragmentation was used for the analysis of apoptosis.Conclusion : The results indicate that local anesthetics with high lipophilicity are highly toxic and induce mainly necrosis, while local anesthetics with low pKa induce more apoptosis.