摘要
Objective To optimize the therapeutic dosage of tetrandrine (Tet) in rat hepatic fibrosis roodel. Methods 50 Wistar rats were divided into 5 groups at random including normal control, model control, Tettreated model groups of 10mg· kg^ - 1· d^ - 1, 5mg· kg^ - 1· d^ - 1 and 2.5mg· kg^ - 1· d^ - 1( n = 10 in each group ). All rats, except for the normal controls, were injected with axenic porcine serum (0. 5ml each time, twice a week) intraperitoneally for 8 weeks to establish hepatic fibrosis. After the 8th week, rats of Tet-treated model groups were given by gavage once a day with different doses of Tet for another 8 weeks. Then the liver function, serum levels of hyaluronic acid ( HA ), laminin ( LM), and procollagen type Ⅲ (PCⅢ) were tested. Collagen type 1 and Ⅲ, pathological changes in liver tissue were also assessed. Results Most indices of liver function including alanine minotransferase (ALT), aspartate aminotransferase (AST), albumin ( ALB), albumin/globulin ratio ( A/G) and alkaline phosphatase (ALP) improved significantly in Tet-treated groups with the exception of γ-glutamyl transpeptidase (γ- GT) and total bilirubin (TBIL). Secondly, markedly lowered levels of HA, LM and collagen type I, III were also detected by radioimmunology and immunohistochemistry in the 5 mg· kg^ - 1· d^ - 1 Tet-treated model group. Moreover, pathologi- cal findings confirmed the statistically significant improvement in hepatofibrotic degree resulted from the treatment of 5mg· kg^ - 1· d^ - 1 rather than other doses of Tet. Conclusion For experimental Wistar rats, Tet exhibited an anti-hepatofibrotic action in doses within the range of 2.5mg· kg^ - 1· d^ - 1 to 10mg· kg^ - 1· d^ - 1 and 5mg· kg^ - 1· d^ - 1 may be the optimum one among all doses.
Objective To optimize the therapeutic dosage of tetrandrine (Tet) in rat hepatic fibrosis mod- el. Methods 50 Wistar rats were divided into 5 groups at random including normal control, model control, Tel-treated model groups of 10mg·kg-1·d-1, 5mg·kg-1·d-1 and 2. 5mg·kg-1·d-1(n =10 in each group). All rats, except for the normal controls, were injected with axenic porcine serum (0. 5ml each time, twice a week) intraper-itoneally for 8 weeks to establish hepatic fibrosis. After the 8th week, rats of Tet-treated model groups were given by gavage once a day with different doses of Tet for another 8 weeks. Then the liver function, serum levels of hyaluronic acid (HA) , laminin (LM) , and procollagen type III(PCIII) were tested. Collagen type I and III pathological changes in liver tissue were also assessed. Results Most indices of liver function including alanine minotrans-ferase (ALT) , aspartate aminotransferase (AST) , albumin (ALB) , albumin /globulin ratio (A/G) and alkaline phosphatase (ALP) improved significantly in Tet-treated groups with the exception of γ-glutamyl transpeptidase (γ-GT) and total bilirubin ( TBIL). Secondly, markedly lowered levels of HA, LM and collagen type I, III were also detected by Tadioimmunology and immunohistochemistry in the 5mg·kg-1·d-1Tet-treated model group. Moreover, pathological findings confirmed the statistically significant improvement in hepatofibrotic degree resulted from the treatment of 5mg ·kg-1·d-1 rather than other doses of Tet. Conclusion For experimental Wistar rats, Tet exhibited an anti-hepat-ofibrotic action in doses within the range of 2. 5mg·kg-1·d-1to 10mg·kg-1·d-1,and 5mg·kg-1·d-1may be the optimum one among all doses.