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，可诱导细胞凋亡，但局麻药的种类和诱导凋亡的速率尚不清楚。本研究的目的是阐明诱导凋亡或坏死的局麻药及其诱导相关因素。研究方法：评价利多卡因、甲哌卡因、布比卡因、罗哌卡因、丁卡因、地布卡因、普鲁卡因和QX-314在HL-60人白血病细胞系中的凋亡和坏死。用碘化丙啶（PI）和膜联蛋白-V双染色法分析细胞凋亡和坏死，并通过流式细胞术（FACS）进行测量。结论：高亲脂性局麻药毒性强，主要诱导细胞坏死，低pKa局麻药诱导细胞凋亡较多。

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.