A Discussion on the Relationship among Hepatic Stellate Cells,Hepatic Sinusoidal Endothelial Cells and Hepatic Sinusoidal Capillarization in the Development of Hepatic Fibrosis

Hepatic stellate cells,hepatic sinusoidal endothelial cells and hepatic sinusoidal capllarization are closely related to the occurrence and progression of hepatic fibrosis.The pathological activation of hepatic stellate cels is the central link of hepatic fibrosis,and hepatic sinusoidal capillarization also promotes the occurrence and development of liver diseases.In the course of hepatic fibrosis,there is always a mutually reinforcing relationship between the activation of hepatic stellate cells and the capillarization of hepatic sinusoids.This paper strives to find an effective way to intervene or even reverse this vicious cycle by deeply investigating the effect of hepatic stellate cells and hepatic sinusoidal capillarization on hepatic fibrosis and their mutual promotion,and provide a new idea for the treatment of hepatic fibrosis,which is of great significance for relieving and reversing hepatic fibrosis.

Research Progress on the Regulation of Hepatic Sinusoidal Endothelial Cells on Hepatic Fibrosis

Hepatic sinusoidal endothelial cell is a highly differentiated cell in hepatic sinusoid,and plays an important role in the occurrence and development of hepatic fibrosis.The dysfunction of hepatic sinusoidal endothelial cells is considered to be the key cause of a variety of liver diseases.At present,the researches on hepatic fibrosis at home and abroad are mainly focused on inhibiting the activation of hepatic stellate cells and accelerating the hydrolysis of extracellular matrix.However,there are few studies on the important role of the structure and function of hepatic sinusoidal endothelial cells in hepatic fibrosis.This paper reviews the research progress on the effect of hepatic sinusoidal endothelial cells on hepatic fibrosis and its regulatory mechanism in recent years.This paper summarizes the results of the research on the structural characteristics of hepatic sinusoidal endothelial cells,secretion of fibrosis-related cytokines and regulation of hepatic stellate cells activation in the development of hepatic fibrosis.

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

AIM： To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS： Fifty SD rats were divided into control group （n=20） and model group （n=30）. Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole （1 000：250：3）. Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid （HA）, type IV collagen （COW） and laminin （LN） were determined by radioimmunoassay. Liver tissue was fixed in formalin （10%） and 6-μm thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polydonal antibody against LN and ColⅣ. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. RESULTS： The diameter （2.207 ± 0.096 vs 1.528±0.054 mm, P〈0.01） and pressure （11.014±0.395 vs 8.533±0.274 mmHg, P〈0.01） of portal vein were significantly higher in model group than those in the control group. Plasma HA （129.97±16.10 vs 73.09±2.38 ng/mL, P〈0.01）, ColⅣ （210.49±4.36 vs 89.65±4.42 ng/mL, P〈0.01） and LN （105.00±7.29 vs 55.70±4.32 ng/mL, P〈0.01） were upregulated in model group. Abundant collagen deposited around the central vein of Iobules, hepatic sinusoids and hepatocytes in model group. ColⅠ and ColⅢ increased remarkably and perisinusoids were almost surrounded by ColⅢ. Immunohistochemical staining showed that ColⅣ protein level （0.130±0.007 vs 0.032±0.004, P〈0.01） and LN protein level （0.152±0.005 vs 0.029±0.005, P〈0.01） were up-regulated remarkably in model group. MMP-2 protein expression （2.306±1.089 vs 0.612±0.081, P〈0.01） and TIMP-1 protein expression （3.015±1.364 vs 0.446±0.009, P〈0.01） in freshly isolated hepatic nonparenchymal cells were up-regulated in model group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression （2.669±0.170 vs 1.695±0.008, P〈0.05）. CONCLUSION： Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are responsible for alcoholinduced portal hypertension in rats,

Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis

Objective:To screen the active components from Fuzheng Huayu Recipe(FZHY)and redesign a new recipe composed of the active components,and validate the effect of active components formulation from FZHY against liver fibrosis.Methods:Thirty-two components from FZHY were evaluated for their activities against liver fibrosis respectively,with 6 kinds of cell models in vitro,including oxidative stressed hepatocyte in L-02,hypoxia injured/proliferative hepatic sinusoidal endothelial cells in SK-HEP-1 and human hepatic sinusoidal endothelial cells(HHSEC),and activated hepatic stellate cell in LX-2.The comprehensive activity of each component against liver fibrosis was scored according to the role of original herbs in FZHY and cell functions in fibrogenesis.Totally 7 active components were selected and combined with equal proportion to form a novel active components formulation(ACF).The efficacy of ACF on liver fibrosis were evaluated on activation of LX-2 and proliferation of HHSEC in vitro and in liver fibrosis model mice induced by dimethylnitrosamine(DMN).Totally 72 mice were divided into6 groups using a random number table,including normal,high-dose ACF control(20μmol/L×7 components/kg body weight),model,low-,medium-,high-dose ACF groups(5,10,20μmol/L×7 components/kg body weight,respectively).Hematoxylin eosin and Sirius red stainings were used to observe inflammation and fibrosis change of liver tissue;scanning electron microscopy(SEM)and transmission electron microscopy(TEM)were utilized to observe the effect of ACF on ultrastructure of hepatic sinusoids.Results:Fifteen components from FZHY showed higher scores for their activity on against liver fibrosis.Among them,7 components including tanshinoneⅡA,salvianolic acid B,cordycepin,amygdalin,quercetin,protopanaxatriol,and schizandrin B were recombined with equal proportions to form ACF.ACF at 1,2,4μmol/L showed strong inhibitory effects on activation of LX-2 and proliferation of HHSEC in vitro(all P<0.01).Compared with the model group,ACF attenuated liver collagen deposition,improved sinusoidal capillarization in a dose-dependent manner(all P<0.05).Conclusions:ACF exerts a satisfactory effect against experimental liver fibrosis and attenuates sinusoidal capillarization,which warrant a further research and development for herbal components formulation on liver fibrosis.