目的研究蟾毒灵的镇痛作用及其作用机制, 为其临床应用提供理论依据。方法 通过醋酸诱发小鼠扭体反应实验和小鼠热板实验, 研究蟾毒灵的镇痛作用, 通过Griess法和免疫印迹法研究RAW264.7细胞中NO含量和MAPK/p38/iNOS通路的变化。结果 蟾毒灵(0.5 mg/kg、1.0 mg/kg)可以剂量依赖性地减少醋酸所致的小鼠扭体数(P<0.05), 并可显著提高热板所致疼痛小鼠痛阈值(P<0.05)。体外研究表明蟾毒灵(0.04 μM, 0.08 μM)可显著降低脂多糖(LPS)诱导的RAW264.7细胞的NO含量升高(P<0.05), 并可以抑制RAW264.7细胞的MAPK/p38/iNOS信号通路的激活。结论 蟾毒灵具有一定的镇痛作用, 其镇痛机制可能与抑制MAPK/p38/iNOS通路, 继而减少NO的合成和释放有关。

Objective To investigate the analgesic effect of bufalin and its underlying mechanisms. Methods The analgesic effect of bufalin was studied by the acetic acid-induced writhing response and hot plate test. The contents of NO and the activation of MAPK/p38/iNOS pathway in LPS-induced RAW264.3 were measured by Griess assay and Western blotting, respectively. Results Bufalin (0.5, 1.0 mg/kg) showed a significant inhibition of acetic acid-induced writhing response and prolonging of licking time in hot plate test at a dose-dependent manner (P<0.05). Bufalin (0.04, 0.08 μM) significantly reduced the contents of NO and inhibited the activation of MAPK/p38/iNOS in RAW264.7 cells. Conclusions The analgesic of bufalin is related to suppressing the activation of MAPK/p38/iNOS pathway and subsequently reducing the synthesis and releases of excessive NO.