Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure.
Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure.
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DOI：
10.1016/j.jhep.2016.11.017
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发表时间：
2017-04
影响因子：
25.7
通讯作者：
Jaeschke H
中科院分区：
文献类型：
--
作者：
Woolbright BL;Jaeschke H
药物引起的急性肝衰竭具有很高的发病率和死亡率。对乙酰氨基酚过量是急性肝功能衰竭的头号原因，仍然是西医的一个主要问题。N-乙酰半胱氨酸的管理是一种有效的解毒剂时，在最初的毒性上升之前给予;然而，许多患者在这个阶段发生后到医院就诊。因此，治疗，可以减轻晚期对乙酰氨基酚诱导的急性肝衰竭是必要的。虽然最初的毒性机制得到了很好的描述，但最近在文献中发生了关于是否存在由炎症过程介导的损伤的第二阶段的争论。这种潜在的炎症过程的关键是被称为炎性体的分子复合物激活半胱天冬酶-1和白细胞介素-1 β。已经鉴定了用于形成多种不同炎性小体复合物的许多不同刺激物。特别是Nalp 3炎性小体的形成直接归因于晚期对乙酰氨基酚毒性。本文就对乙酰氨基酚致小鼠和人肝损伤的机制进行综述，重点介绍炎症和炎性小体在肝损伤中的作用。
Drug-induced acute liver failure carries a high morbidity and mortality rate. Acetaminophen overdose is the number one cause of acute liver failure and remains a major problem in Western medicine. Administration of N-acetyl cysteine is an effective antidote when given before the initial rise in toxicity; however, many patients present to the hospital after this stage occurs. As such, treatments which can alleviate late-stage acetaminophen-induced acute liver failure are imperative. While the initial mechanisms of toxicity are well described, a debate has occurred recently in the literature over whether or not there exists a second phase of injury, mediated by inflammatory processes. Critical to this potential inflammatory process is the activation of caspase-1 and interleukin-1ß by a molecular complex known as the inflammasome. A number of different stimuli for formation of multiple different inflammasome complexes have been identified. Formation of the Nalp3 inflammasome in particular has directly been attributed to late-stage acetaminophen toxicity. In this review, we will discuss mechanisms of acetaminophen-induced liver injury in mice and man with a particular focus on the role of inflammation and the inflammasome.