ABSTRACT: The serum level of hyaluronic acid (HA) has been suggested as a useful serologic marker for hepatic fibrosis. However, the relationship between serum HA levels and quantitative markers of fibrosis from liver tissue has not been reported. The aim of this study was to determine the correlation between serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic rat model.
Cirrhosis was produced by common bile duct ligation (BDL) in adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1, sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed histomorphologically using the Batts and Ludwig scoring system. Serum HA level and hepatic hydroxyproline content were quantified. The gene expressions in the liver of procollagen, collagen, and transforming growth factor-beta (TGF-beta) were measured by reverse transcriptase-polymerase chain reaction.
In groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean+/-SD) were 0, 1.3+/-0.5, 2.6+/-0.5, and 3.4+/-0.5, respectively (P<0.05), serum HA levels were 12.5+/-3.2, 30.0+/-4.3, 228.6+/-157.7, and 391.3+/-207.7 ng/mL (P<0.05), and the concentration of hydroxyproline was 12.4+/-2.8, 17.6+/-3.8, 17.9+/-2.4, and 33.4+/-3.4 microg/g liver tissue, and it was significantly higher in group G4 than in the other groups (P<0.05). The gene expressions of collagen, procollagen, and TGF-beta1 in the liver were also significantly higher in group G4 compared with the other groups (P<0.05). Direct linear correlations were observed between serum HA level and hepatic hydroxyproline content, hepatic gene expressions of collagen, procollagen, TGF-beta1, and histomorphological grade of hepatic fibrosis (P<0.001).
These results indicate that serum HA is a useful and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis.
The Korean Journal of Hepatology 06/2008; 14(2):159-67.
ABSTRACT: Angiotensin blockade such as with an angiotensin II receptor blocker (ARB) or angiotensinconverting enzyme inhibitor (ACEI) has antifibrotic properties. The aim of this study was to evaluate and compare the antifibrotic effect between ARBs and ACEIs.
Common bile duct-ligated (BDL) adult Sprague-Dawley rats were allocated to five groups (each group, n = 8) as follows: G1, BDL without drug; G2, BDL + captopril 100 mg/kg per day; G3, BDL + ramipril 10 mg/kg per day; G4, BDL + losartan 10 mg/kg per day; G5, BDL + irbesartan 15 mg/kg per day. Four weeks post-BDL, hepatic fibrosis was analyzed histomorphologically using Batts and Ludwig scores. alpha-Smooth muscle actin (alpha-SMA) expression by immunohistochemical staining, hydroxyproline contents of liver tissue by spectrophotometry, and angiotensin receptor, collagen, procollagen, and transforming growth factor beta (TGF-beta) expressions were evaluated by real-time reverse transcriptase-polymerase chain reaction. Angiotensin receptor expression was also determined by Western blotting.
Batts and Ludwig scores were 3.8, 2.6, 2.4, 1.8, and 1.6 in G1, G2, G3, G4, and G5, respectively. Histologically, ARB groups (G4, G5) showed significant suppression of hepatic fibrosis compared with ACEI groups or the control. Expressions of alpha-SMA (%) and the content of hydroxyproline (microg liver tissue) were significantly lower in ARB groups (G4, G5) than in ACEI groups (G2, G3) (P < 0.05). Also, ARB reduced the expression of angiotensin receptor, collagen, procollagen, and TGF-beta1 compared with ACEI. Western blot analysis showed that the expression of angiotensin receptor was inhibited in both ARB and ACEI groups.
Both ARB and ACEI attenuate hepatic fibrosis through inhibiting hepatic stellate cell activation, and the inhibitory effect of ARBs on hepatic fibrosis is superior to that of ACEIs in the BDL rat model.
Journal of Gastroenterology 01/2008; 43(11):889-96. · 4.16 Impact Factor
ABSTRACT: Angiotensin receptors are found on hepatic stellate cells, which participate in hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model. Material and
Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL) in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100 mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. alpha smooth muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and expression of collagen, procollagen, and TGF-beta by real-time PCR were measured.
Batts & Ludwig score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively (p<0.05). The concentration of hydroxyproline (microg/g liver tissue) was lower in G3 and G4 compared with G1 (p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression of collagen, procollagen, and TGF-beta mRNA.
Angiotensin blockades are effective in the prevention of hepatic fibrosis in BDL rats.
The Korean Journal of Hepatology 04/2007; 13(1):61-9.