Effect Of Hepatic Chymase In Liver Fibrosis And Its Mechanism

Chapter1 Hepatic chymase content in chronic hepatic diseases relationship to fibrosis1. Hepatic chymase content in chronic hepatitis relationship to fibrosisObjective:To investigate spatial relatioship between human chymase and fibrosis in liver specimens affected by chronic hepatitis. Methods:The chymase levels were determined by using the method of enzyme-linked immunosorbant assay (ELISA) in 45 cases of chronic hepatitis. Mast cell distribution in the specimens was determined immunohistochemically using anti-chymase antibudy. Results:①Hepatic chymase concentrations in S3 and S4 cases were greater than in S1 and S2. Hepatic chymase contentrations in S3+S4 cases were greater than that in S1+S2(S3+S4= 31.3±24.6ng/mg vs. S1+S2= 5.7±4.8ng/mg; P<0.01).②Hepatic chymase concentrations in G3 and G4 cases were greater than in G1 and G2. Hepatic chymase concentrations in G3+G4 cases were greater than that in G1+G2 (G3+G4=30.58±23.53 ng/mg vs. G1+G2=6.39±4.93ng/mg; P<0.01).③Cells immunoreactive for chymase were seen throughout portal areas and intralobular sinusoidal walls, largely colocalizing with fibrosis.Conclusion:Chymase appears to be involved in hepatic fibrosis in chronic hepatitis. 2. Increased Chymase in Livers with Autoimmune Disease: Colocalization with FibrosisObjective To investigate spatial relatioship betwwen human chymase and Fibrosis in liver specimens affected by autoimmune hepatitis (AIH) or primary biliary cirrhosis(PBC). Methods The chymase levels were determined by using the method of enzyme-linked immunosorbant assay(ELISA) in 15 cases of AlH and 14 cases of PBC.11 cases of acute hepatitis(AH) were used as control. Mast cell distribution in the specimens was determined immunohistochemically using anti-chymase antibudy. Results The mean amounts of chymase in livers with AlH and PBC were 15.53±4.89ng/mg and 12.67±3.69ng/mg respectively. Hepatic chymase in AIH and PBC was significantly more abundant than in AH(2.72±1.02ng/mg),P<0.01. When sections from patients with AlH and PBC were immunostained for chymase, immunoreactive mast cells were detected in portal areas and sinusoidal walls, coinciding with zones of fibrosis. Conclusion Chymase appears to be involved in hepatic fibrosis in AIH and PBC.3. Increased Chymase in Livers with Alcoholic Liver Fibrosis:Colocalization with FibrosisObjective To investigate spatial relationship between human chymase and Fibrosis in liver specimens affected by alcoholic liver fibrosis(ALF). Methods The chymase levels were determined by using the method of enzyme-linked immunosorbant assay(ELISA) in 28 cases of ALF and 11 cases of acute hepatitis(AH) used as control. Mast cell distribution in the specimens were determined immunohistochemically using anti-chymase antibudy. Results The mean amounts of chymase were 17.53±4.39ng/mg in ALF and 2.81±1.03ng/mg in acute hetatitis, respectivly. Hepatic chymase in ALF were significantly more abundant than in AH, P<0.01. When sections from patients with ALF were immunostained for chymase, immunoreactive mast cells were detected in areas around hetatic cell and central vein, coinciding with zones of fibrosis. Conclusion Chymase appears to be involved in hepatic fibrosis in alcoholic liver fibrosis.Chapter2 Chymase inhibitor in the rat model of dimethylnitro-samine(DMN)-induced liver fibrosis and its impact on the expression of angiotensin II and collagen I Objective:To study the effect of chymase inhibitor on dimethyin-itrosamine (DMN)-induced liver fibrosis in rats and its possible mechanism. Methods: seventy six rats were randomly divided into three groups:the model group, the control group and the chymase inhibitor treatment group, in which the rats were given intraperitoneal injections of 1%DMN(1ml/mg). From the first day after DMN challenge, by evry day,the chymase inhibitor treatment group was perfused intostomach daily chymase inhibitor(10mg/kg) for 42 days, the other group were given sterile saline. Liver tissue samples were examined on 10,17,28,56 days. Histopathological study of liver tissue was perfomed with hematoxylin-eosin(HE) and Masson trichrome staining. The chymase levels were determined by using the method of enzyme-linked immunosorbant assay (ELISA). The levels of angiotensin II in the liver were determined by radioimmunoassay(RIA). The collagen type I (Col-Ⅰ) were evaluated by reverse-transcription polymerase chain reaction (RT-PCR). Results:①Liver fibrosis was evidently inhibited after chymase inhibitor treatment.②The levels of chymase and chymase mRNA expression in the liver were evidently inhibited after chymase inhibitor treatment, and they were higher in the liver fibrosis of the model group than in the control group, also they were significantly lower in the chymase inhibitor group.③The levels of angiotensinⅡand Col-Ⅰwere evidently inhibited after chymase inhibitor treatment, and they were higher in the liver fibrosis of the model group than in the control group, also they were significantly lower in the chymase inhibitor group. Conclusion: Chymase inhibitor can alleviate dimethylnitrosamine-induced liver fibrosis in rat by inhibiting chymase activity and chymase mRNA expression, and by inhibiting angiotensin II, Col-I in the liver tissues.Chapter3 Effect of varsartan on serum transforming growth factor-beta-1, hyaluronic acid and cholylglycine in patients with hepatic cirosis Objective To investigate effects of valsartan of serum transforming growth factor-beta 1(TGF-β1), Hyaluronic acid(HA) and cholyglycine(CG) in cirrhosis patients. Methods Forty cirrhosis patients were randomized into control group and treatment group. Twenty patients in control group received routine treatment for 3 months and twenty patients in treatment group received valsartan 80 mg/d based on routine treatment for 3 months. Before and after treatment, serum TGF-β1 was measured by enzyme-linked immunosorbantassay(ELISA),and the levels of HA and CG were measured by radioimmunoassay. Results In valsartan group, the levels of TGF-β1, HA and CG were lower after treatment than that before treatment(P<0.01). In control group, the levels of TGF1-β, HA and CG were lower after treatment than that before treatmen, but there was no significant difference(P>0.05). The differences of TGF-β1, HA and CG were lower after treatment and after treatment between two groups were statistically significant (P<0.01). Conclusion Valsartan can decrease the levels of TGF-β1, HA and CG, which may improve hepatic fibrosis in cirrhosis patients to some extent.