| Objective:Explore variation on expression of angiotensin converting enzyme (ACE) and angiotensin converting enzyme2(ACE2), level of angiotensin Ⅱ (Ang Ⅱ) and angiotensin(1-7)(Ang(1-7)), ratio of Ang Ⅱ/Ang(1-7) in the formation of cirrhotic rats and intervention effect of valsartan so as to discuss relationship between the RAS members and Losartan possible anti fibrosis mechanism.Methods:52Wistar rats were randomly divided into three groups:a normal group (n=12), a model group (n=34), a treatment group (n=6). Cirrhosis rats model were induced by compound factors, altogether56days.6rats in the model group were killed at2,4,6and8weeks respectively, set blood and liver tissues aside. The treatment group was given losartan (20mg/kg/d) through irrigation stomach after the model made for14days. Take other random six rats in the normal group and model group as control groups, given irrigation stomach with the same amount of distilled water. Portal vein pressures were examined for each group after treatment. Histo-pathological study of the liver tissues was done with hematoxylin-eosin (HE) and masson trichrome staining (Masson). Expressions of ACE and ACE2in liver tissue were evaluated by immunohistochemistry. Ang II and Ang(1-7) levels of liver homogenates were determined by enzyme-linked immunosorbent assay (ELISA).Results:(1)Pathological results:compared with normal group, with the extension of moding time, the degree of liver fibrosis was increasing in model group. The pseudolobules of rats were formed at the end of8weeks of model group. Compared with8w model group, the degree of liver cirrhosis and fibrosis have different levels of ease in treatment group.(2)The portal vein pressure results:compared with the normal control group, portal vein pressure is clearly rising in8w model group (10.68±2.03)(P<0.01); compared with8w model group, portal vein pressure significantly reduced in treatment group (8.09±1.48)(P<0.05); mean arterial pressure and heart rate had no change.(3)ACE, ACE2immunohistochemical results:positive expression of ACE, ACE2are less in normal group liver tissues, ACE expression of6,8w model group and ACE2expression of2,4,6,8w model group are significantly increased than the normal group; compared with8w model group, positive express of ACE had no change in8w model group, while ACE2further increase (18.87±2.95)(P<0.05).(4) ELISA results on Ang Ⅱ, Ang(1-7) and AngⅡ/Ang(1-7) of liver homogenate:compared with normal group, Ang Ⅱ level of6,8w model group and Ang(1-7) levels of2,4,6,8w model group significantly increased, while Ang Ⅱ/Ang(1-7) ratio of2,4w model group decreased (P<0.05); compared with8w model group, AngⅡ level had no change in treatment group, while Ang(1-7) further increased (121.85±26.03) and AngⅡ/Ang(1-7) decreased (1.27±0.31)(P<0.05).Conclusion:The occurrence and development of hepatic fibrosis and cirrhotic rats are possibly associated with imbalanced component in reninangiotensin system (RAS), imbalance between Ang Ⅱ and Ang(1-7). Valsartan can delay the progression of hepatic fibrosis and reduce portal pressure indirectly in cirrhotic rats. The mechanism of its action probably related with increase of ACE2expression and improvement of Ang(1-7) level. |
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