Study On Effect Of Yi-Gan-Kang Decoction-inhibited Proliferation And Collagen Synthesis In Rat HSCs From Different Levels Of Signal Transduction

Hepatic fibrosis represents a repairable process of chronic hepatic damage including viral infections, toxic damage, alcohol, as well as autoimmune reactions. The activation and proliferation of hepatic stellate cells (HSCs)(major collagen-synthesizing cells)are key links of liver fibrosis. In normal liver, HSCs undergo the quiescent state, and synthesize low levels of matrix proteins. But, as a result of liver injury, HSCs are the process of activation, proliferation and transform to myofibroblast-like cells. Through increased secretion of extracellular matrix proteins (particularly typeⅠ,Ⅲcollagen) and tissue inhibitors of matrix metalloproteinases (TIMPs), activated HSCs are responsible for deposition and accumulation of the majority of the excess extracellular matrix (ECM) in fibrotic liver. The increasing of production and secretion of ECM and the decreasing of degradation of them result in the accumulation of ECM and generate fibrosis.IL-1 is a pro-inflammatory cytokine that has a key role in the inflammatory response and in autoimmune diseases. Some researches indicated that IL-1 is accepted as a potent cytokine for fibrosis of other organs such as heart, gingival tissue, and kidney. Recent findings in our laboratory also suggested that IL-1βcould up-regulate proliferation,type I collagen synthesis and expression of TIMP-1 mRNA in rat HSCs.Mitogen-activated protein kinase (MAPK)plays an important role in the transduction of extracellular signals to the nucleus. Four groups of the mammalian MAPK-family have been characterized: the extracellular signal-regulated kinase(ERK), c-jun N-terminal kinase(JNK), p38 and ERK5. Many researchers indicated that JNK and p38 are essential members of MAPK supper family and have a role in the responses of HSCs to hepatic...