对乙酰氨基酚致急性肝损伤中的c-Jun氨基末端激酶信号通路

c-Jun N-terminal kinase signaling pathway in acetaminophen-induced liver injury

对乙酰氨基酚(APAP)是最常见的解热镇痛抗炎药,但过量使用往往会导致急性肝损伤,甚至急性肝衰竭,严重者会造成死亡,目前仍缺乏特异的治疗手段。c-Jun氨基末端激酶(JNK)信号通路是近年来识别出的在过量APAP诱导的急性肝损害中极具潜力的治疗靶点之一。本文从APAP在肝脏代谢过程中的JNK信号通路、JNK信号通路的激活及氧化应激的放大、与JNK信号通路相关的其他通路或细胞过程、靶向JNK的药物可能面临的挑战等方面进行综述,以期为后续JNK信号通路靶点在APAP肝毒性中的进一步研究和临床应用提供方向并进行可行性分析,且为寻找其他靶点提供参考。

Acetaminophen(APAP)is the most common antipyretic,analgesic and anti-inflammatory drug,but its overdose often leads to acute liver injury,even acute liver failure,and death in some severe cases.At present,there is still a lack of specific treatments.The c-Jun N-terminal kinase(JNK)signal pathway is one of the potential therapeutic targets identified in recent years in overdose APAP-induced acute liver injury.This article reviews the JNK signaling pathway of APAP in liver metabolism,the activation of JNK signaling pathway and the amplification of oxidative stress,other pathways or cellular processes related to JNK signaling pathway,and the possible challenges of drugs targeting JNK,so as to provide direction and feasibility analysis for further research and clinical application of JNK signaling pathway targets in APAP hepatotoxicity,and to provide reference for searching for other targets.