Kupffer细胞在肝纤维化形成与转归中的作用

The roles of Kupffer cells in the development and regression of liver fibrosis

肝纤维化是由于反复肝损伤引起持续性炎症反应、瘢痕组织形成,导致正常组织结构破坏甚至器官衰竭的一类疾病。临床研究和动物实验均证实,肝脏内慢性长期炎症是导致过量瘢痕形成的主要诱因。在肝损伤期,Kupffer细胞快速激活并释放大量可溶性调节因子(包括过氧化物、细胞因子和蛋白酶等),刺激肝星状细胞增殖、迁移和活化。另一方面,有研究显示,Kupffer细胞还参与肝纤维化转归,其功能可能与调节星状细胞的生物学活性及促进细胞外基质的降解有关。因此,深入研究Kupffer细胞的生物学特性以及在细胞因子环境下与星状细胞间的相互作用,对于理解肝纤维形成的病理学过程和肝纤维化转归的生理学机制具有重要的指导意义。

Hepatic fibrosis results from iterative hepatic injury with sustained inflammation, formation of scar tissue, loss of tissue architecture and organ failure. There is no doubt, from both human and animal studies, that too much or too protracted inflammation in the liver leads to excess scarring. During liver injury, Kupffer cells can quickly flood the hepatic milieu with soluble mediators, including oxidants, cytokines, and proteinases, which can affect stellate cell proliferation, migration, and differentiation. On the other hand, the contribution of Kupffer cells to regression of hepatic fibrosis has been demonstrated. These findings underscore the potential importance of hepatic macrophages in regulating both stellate cell biology and extracellular material degradation during regression of hepatic fibrosis. Therefore, biological characterization of Kupffer cells, their interactions with stellate cells in the cytokine environment are essential to understand the mechanisms underlying the progressive development of excessive scarring in the liver as well as the ability of the liver for tissue repair and recovery.