Objective:To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model,and the underlying mechanisms were partly dissected in vivo and in vitro.Methods:Thirty-two male mice were randomly divide...Objective:To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model,and the underlying mechanisms were partly dissected in vivo and in vitro.Methods:Thirty-two male mice were randomly divided into 4 groups,including control,model,low-and high-dose amygdalin-treated groups,8 mice in each group.Except the control group,mice in the other groups were injected intraperitoneally with 10%carbon tetrachloride(CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis.At the first 3 weeks,amygdalin(1.35 and 2.7 mg/kg body weight)were administered by gavage once a day.Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week.At the end of 6 weeks,liver tissue samples were harvested to detect the content of hydroxyproline(Hyp).Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue.The expressions of collagenⅠ(Col-Ⅰ),alpha-smooth muscle actin(α-SMA),CD31 and transforming growth factorβ(TGF-β)/Smad signaling pathway were detected by immunohistochemistry,quantitative real-time polymerase chain reaction and Western blot,respectively.The activation models of hepatic stellate cells,JS-1and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin(0.1,1,10μmol/L).The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells(LSECs)dedifferentiation markers CD31 and CD44 were observed.Results:High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area,and decreased the mRNA and protein expressions of Col-Ι,α-SMA,CD31 and p-Smad2/3 in liver tissues of mice compared to the model group(P<0.01).Amygdalin down-regulated the expressions of Col-Ⅰandα-SMA in JS-1 and LX-2 cells,and TGFβR1,TGFβR2 and p-Smad2/3 in LX-2 cells compared to the model group(P<0.05 or P<0.01).Moreover,1 and 10μmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group(P<0.05 or P<0.01).Conclusions:Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway,consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.展开更多
This article presented an overview of the therapeutic effects of Chinese medicine(CM)preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis(PVT)after splenectom...This article presented an overview of the therapeutic effects of Chinese medicine(CM)preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis(PVT)after splenectomy.Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension(CPH),this paper evaluated the incidence of PVT,and explored potential active components and mechanisms of CM preparations.Safflower Yellow Injection,Danshen Injection,Danhong Injection,and Compound Danshen Dropping Pill achieved good curative effect alone or combined with anticoagulant therapy.In addition,Compound Biejia Ruangan Tablet and Anluo Huaxian Pill can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis.Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH,we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.展开更多
基金Supported by National Natural Science Foundation of China(Nos.81530101,81973613 and 81603681)Shanghai Rising-Star Program(No.19QA1408900)。
文摘Objective:To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model,and the underlying mechanisms were partly dissected in vivo and in vitro.Methods:Thirty-two male mice were randomly divided into 4 groups,including control,model,low-and high-dose amygdalin-treated groups,8 mice in each group.Except the control group,mice in the other groups were injected intraperitoneally with 10%carbon tetrachloride(CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis.At the first 3 weeks,amygdalin(1.35 and 2.7 mg/kg body weight)were administered by gavage once a day.Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week.At the end of 6 weeks,liver tissue samples were harvested to detect the content of hydroxyproline(Hyp).Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue.The expressions of collagenⅠ(Col-Ⅰ),alpha-smooth muscle actin(α-SMA),CD31 and transforming growth factorβ(TGF-β)/Smad signaling pathway were detected by immunohistochemistry,quantitative real-time polymerase chain reaction and Western blot,respectively.The activation models of hepatic stellate cells,JS-1and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin(0.1,1,10μmol/L).The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells(LSECs)dedifferentiation markers CD31 and CD44 were observed.Results:High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area,and decreased the mRNA and protein expressions of Col-Ι,α-SMA,CD31 and p-Smad2/3 in liver tissues of mice compared to the model group(P<0.01).Amygdalin down-regulated the expressions of Col-Ⅰandα-SMA in JS-1 and LX-2 cells,and TGFβR1,TGFβR2 and p-Smad2/3 in LX-2 cells compared to the model group(P<0.05 or P<0.01).Moreover,1 and 10μmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group(P<0.05 or P<0.01).Conclusions:Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway,consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.
基金Supported by the National Natural Science Foundation of China(No.81703681,81530101)the Shanghai Sailing Program(No.17YF1419800)。
文摘This article presented an overview of the therapeutic effects of Chinese medicine(CM)preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis(PVT)after splenectomy.Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension(CPH),this paper evaluated the incidence of PVT,and explored potential active components and mechanisms of CM preparations.Safflower Yellow Injection,Danshen Injection,Danhong Injection,and Compound Danshen Dropping Pill achieved good curative effect alone or combined with anticoagulant therapy.In addition,Compound Biejia Ruangan Tablet and Anluo Huaxian Pill can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis.Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH,we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.
