NOXs在肝纤维化中的作用机制研究

Study on mechanism of NOXs in liver fibrosis

还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶(nicotinamide adenine dinucleotide phosphate oxidase,NOXs)在肝纤维化中,有助于活性氧簇(reactive oxygen species,ROS)的产生,进而介导内质网应激(endoplasmic reticulum stress,ERS)的发生及IRE1α-XBP1(inositol-requiring enzyme 1 alpha,IRE1α;X-box binding protein 1,XBP1)信号通路的激活。ROS是指分子氧(O_2)单电子还原后生成的化学性质更为活跃的一类氧代谢产物及其衍生物,包括超氧阴离子(O_2^-)、羟自由基(·OH)、过氧化氢(H_2O_2)以及次氯酸根离子(OCl^-)等。它们可以与生物体内大量分子,包括无机分子、蛋白、脂质、碳水化合物和核酸广泛互作,介导氧化还原修饰,引起脂质过氧化,进而引起肝细胞损伤。另可作为第二信使影响包括肝星状细胞(hepatic stellate cells,HSC)在内的各种细胞的信号转导,导致HSC的异常活化和增殖,分泌大量胞外基质(extracellular matrix,ECM),进而促使肝细胞凋亡并诱发肝纤维化。该文将对近年来NOXs在肝纤维化中的作用机制研究作一综述,旨在为抗肝纤维化的研究提供新的视角和治疗靶标。

Nicotinamide adenine dinucleotide phosphate oxidase( NOXs) contributes to the production of reactive oxygen species( ROS) in liver fibrosis,resulting in the activation of endoplasmic reticulum stress( ERS) and IRE1α-XBP1 signaling pathway. ROS is a series of oxygen metabolites and its derivatives,produced by the single electron reduction of molecular oxygen( O_2),including superoxide anion( O_2^-),hydroxyl radical(-OH),hydrogen peroxide( H_2O_2),hypochlorite ion( OCl^-)and so on. They can interact with a large number of molecules,including small inorganic molecules,proteins,lipids,carbohydrates and nucleic acids,resulting in lipid peroxidation of cell damaging molecules. And as a second messenger,ROS can also affect the proliferation and activation of HSC in liver fibrosis,and induce the hepatocyte apoptosis through a variety of cellular signal transduction. Here we review the current status of the study on the mechanism of NOXs in liver fibrosis.