The Effect Of Cell Junction Of Hepatic Stellate Cell On The Pathological Process Of Hepatic Fibrosis In Rat

Background:Liver fibrosis is a common pathway of multiple chronic liver diseases,which is characterized by excessive and abnormal deposition of extracellular matrix.The mechanism of hepatic fibrosis have been deeply studied,hepatic stellate cells(HSCs)play a central role in the development of liver fibrosis.Response to chronic liver injury from a variety of causes including alcohol,autoimmune,viral and so forth,these quiescent HSCs transdifferentiate into proliferative,contractile myofibroblast-like phenotypes,as represented by the expression of a-SMA and by the production of excessive extracellular matrix,thereby accelerating the progression of liver fibrosis.The study of the active mechanism has been focused on the role of various cytokines,and the antifibrotic therapies by inhibiting cytokines expression,but these antifibrotic therapies haven't get the ideal therapeutic effect,so there must have ignored the other active mechanism besides cytokines.The pathomorphology and feature of the rat model liver fibrosis induces by CCL4 are similar to human liver fibrosis,so we use the rat model to investigate the active mechanism of hepatic stellate cell.Objective:To investigate the effect of the hepatic stellate cell junction to the pathological process of liver fibrosis by CCL4-induced liver fibrosis model of rat.Methods:28 SD rats were divided into liver fibrosis model group(n=24)and control group(n=4).The rats in liver fibrosis model group were gavaged the mixture of carbon tetrachloride(CCL4,40%)and olive oil(60%)by 1.0ml/1.0kg,twice a week for 12 weeks.The control group were gavaged the same volume of Distilled water in the same time and route as the liver fibrosis model group.The HE staining was used for observing the liver inflammation infilteration,and the Masson staning was used for observing liver fibrosis.We use immunohistochemistry fluorescence to detect the expression of Desmin and ?-SMA,and observe the morphology change and distribution of active HSCs.Result: 1.There are no active HSCs in normal liver tissue(G0S0),and quiescent HSCs are uniformity distributed in liver sinusoid.2.During the inflammation stage before the formation of hepatic fibrosis(G1S0),HSCs are activited by the stimulate of inflammation,and HSCs are also uniformity distributed in hepatic sinusoid.3.The early stage of hepatic fibrosis(G2S1andG3S2),HSCs are migrated to the inflammatory area and activiation.There are no HSCs in none inflammatory area.4.The stage of form the fibrous septum(S4),HSCs are activated significently than the early stage,they are distributed in liver fibrosis area and perform a model of “head-tail”.Conclusions:The active hepatic stellate cells are the crucial factor to induce liver fibrosis in CCL4-induced rat liver fibrosis model,and the cell junction of hepatic stellate cells are the important condition of form the fibrous septum.