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 endotheli...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.展开更多
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 fib...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.展开更多
基金National Natural Science Foundation of China(81960761,81960751,81902764).
文摘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.
基金Supported by the Major Projects of the Ministry of Science and Technology of China(No.2014ZX10005001)the National Natural Science Foundation of China(No.81603467,81730109)the Third Batch of Open Projects of Shanghai Innovation Center of Traditional Chinese Medicine Health Service(No.ZYJKFW201811013)。
文摘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.
