肝组织学逆转能否实现.ppt

Fibrosis is a consequence of almost all chronic liver diseases predominantly arising from viral, alcohol-induced, autoimmune, and metabolic aetiologies. It describes the result of a dysregulated wound healing response driven by iterative injury and resulting in the balance of extracellular matrix turnover favouring net deposition. Iterative injury is vital in perpetuating this response. The progressive accumulation of matrix ultimately leads to the development of cirrhosis in a proportion of patients with associated important clinical sequelae. A common pathological feature of chronic liver disease is fibrosis which results from unregulated wound-healing and is characterised by the progressive replacement of functional hepatic tissue with highly cross-linked collagen I/III-rich extracellular matrix. For Internal Use Only * The cascade of events leading to hepatic fibrosis is complex, and is influenced by how different cell types in the liver interact in response to injury. The main cell type responsible for the development of fibrosis in chronic liver disease is the activated hepatic stellate cell. Chronically activated hepatic stellate cells proliferate and synthesize extracellular matrix proteins to produce the fibrous scar.肝纤维化的形成是一个级联反应,肝细胞内不同的细胞系对损伤的不同应答及相互之间的作用,都可能会影响肝纤维化的级联反应.活化的HSC细胞在慢性肝病肝纤维化发展中起主要作用,HSC激活以后形成成肌纤维细胞,大量增殖增殖和合成ECM蛋白,从而形成纤维瘢痕.瘦素在HSC细胞转分化过程中也有作用.除了HSC,肝脏原位的间充质干细胞\门管区成纤维细胞\肌成纤维细胞在肝纤维化过程中均有重要的作用.损伤后HSC分化为肌成纤维细胞样表型，具有促纤维化、促炎性、促血管新生等特性。细胞培养研究发现，活化以后的HSC的表型改变包括有增殖能力增加，表达PDGF-B和a-SMA增加，促进胶原分泌增加。 纤维化形成和修复分三个阶段 纤维化形成主要包括两个阶段:起始阶段(initiation)和扩展阶段（perpetuation） 之后若解除肝损，则随之出现肝脏纤维化清除（resolution）阶段 Activated HSCs (Pathogenesis and treatment of hepatic fibrosis: is cirrhosis reversible? clinical medicine 2011): ? lose lipid proliferate ? migrate ? express myogenic markers such as alpha-smooth muscle actin ? produce excessive scar proteins (mostly type-1 collagen) ? demonstrate enhanced contractility and immune capability For Internal Use Only * Fibrosis