炎性小体激活与细胞焦亡及其在酒精性肝病中的研究进展

Progress in inflammasome activation and pyrolysis in alcoholic liver disease

酒精性肝病(alcoholic liver disease,ALD)是一种以脂质在肝中大量积累,伴有炎症、纤维化、肝硬化和肝细胞癌为特征的慢性肝病。在ALD的不同阶段中,免疫系统的介质(如细胞因子或炎性小体)发挥重要的作用。在ALD疾病谱中,炎症级联反应的上调是脂肪性肝炎发展为严重ALD的主要因素。炎症级联反应的激活需要多种刺激。细胞焦亡是近年来发现的一种新的依赖半胱天冬氨酸蛋白酶(caspase)的程序性细胞死亡方式。炎性小体在细胞焦亡的过程中发挥着至关重要的作用。细胞感染或细胞应激能够激活炎性小体,导致炎性小体多蛋白复合物组装、caspase‐1激活及其下游底物白细胞介素-1β前体、白细胞介素-18前体和Gasdermin D活化成熟,从而参与机体的免疫炎性反应及诱导细胞焦亡发生。炎性小体的激活及细胞焦亡可能在ALD的发生、发展中起关键作用。

Alcoholic liver disease(ALD)is a chronic liver disease characterized by large accumulation of lipids in the liver,accompanied by inflammation,fibrosis,cirrhosis,and hepatocellular carcinoma.In the different stages of ALD,mediators of the immune system,such as cytokines or inflammasomes,are crucially involved.In the ALD disease spectrum,the upregulation of the inflammatory cascade is the main factor in the development of steatohepatitis into severe alcoholic hepatitis.Activation of the inflammatory cascade requires multiple stimuli.Pyroptosis is a new type of programmed cell death that relies on caspase.Inflammasomes play a crucial role in the process of cell death.Cellular infection or cellular stress can activate inflammatory corpuscles,leading to assembly of inflammasome polyprotein complexes,activation of caspase-1 and its downstream substrates pro-IL-1β,pro-IL-18 and gasdermin D activation and maturation,thus participating in the body's immune inflammatory response and induced cell death.In recent years,there is increasing evidence that activation of inflammatory bodies and pyroptosis play a key role in the development of alcoholic liver disease.