動物模式評估丹參、柴胡舒肝散單獨使用或與斥消靈合用之抗肝纖維化療效

Anti-liver Fibrotic Effect of Salvia miltiorrhiza and Shugan-Huayu Powder Combining with or without Rapamycin in Animal Models

程景章(Ching-Chang Cheng) ； 李儼峰(Yen-Feng Lee) ； 林雲蓮(Yun-Lian Lin) ； 吳龍源(Lung-Yuan Wu) ； 吳明儒(Ming-Ju Wu) ； 林乃女(Nai-Nu Lin) ； 董光中(Kwong-Chung Tung) ； 邱雲棕(Yung-Tsung Chiu)

《臺灣獸醫學雜誌》 36卷2期 (2010/06) Pp. 141-154

https://doi.org/10.7009/TVJ.201006.0141

摘要

In this study, a rat model of liver fibrosis induced by carbon tetrachioride (CCl4) was used to investigate anti-fibrotic effects of Salvia miltiorrhiza (SM) and Shugan-Huayu powder (SHP), either alone or in combination with rapamycin (Rapa). Liver fibrosis was induced by CCl4 (1.0 mL/kg, by gavage) twice a week for 8 weeks. The CCl4-induced rats were randomly assigned to seven groups: control, CCl4, SM (40 mg/kg/day), SHP (2.52 g/kg/day), Rapa (1.5 mg/kg/day), SM+Rapa and SHP+Rapa. Assessment of anti-fibrotic effects includes clinical signs and body weight, serum biochemistry (AST, ALT, and BUN), histological scoring of liver fibrosis, quantitation of hepatic collagens and α-smooth muscle actin (α-SMA), and zymography for matrix metalloproteinases (MMPs) activity. In clinical signs, Rapa and SM+Rapa group rats revealed remarkable bad appetite, decreased body weight and malnutrition; especially, the mortality of SM+Rapa group was 50%. The contents of AST and ALT in Rapa, Rapa+SM, SHP and Rapa+SHP groups were significantly decreased (P＜0.01, vs CCl4 group). The histopathological examination, scoring of liver fibrosis and determination of hepatic total collagen were significantly reduced in Rapa, Rapa+SM, SHP and Rapa+SHP groups compared to CCl4 group (P＜0.01). α-SMA proteins were markedly reduced in Rapa and Rapa+SM groups (P＜0.001, vs CCl4 group). Decreased MMP-2 activity was noticed in Rapa, Rapa+SM, SHP and Rapa+SHP groups. These results showed anti-fibrotic effects of rapamycin, SM+Rapa, SHP and SHP+Rapa in the rat model of liver fibrosis induced by CCl4. However, the toxity and side effect in Rapa, Rapa+SM were more severe than SHP and Rapa+SHP.

關鍵字

肝纖維化 ； 中西醫藥合併 ； 肝星狀細胞 ； 動物模式

並列摘要

In this study, a rat model of liver fibrosis induced by carbon tetrachioride (CCl4) was used to investigate anti-fibrotic effects of Salvia miltiorrhiza (SM) and Shugan-Huayu powder (SHP), either alone or in combination with rapamycin (Rapa). Liver fibrosis was induced by CCl4 (1.0 mL/kg, by gavage) twice a week for 8 weeks. The CCl4-induced rats were randomly assigned to seven groups: control, CCl4, SM (40 mg/kg/day), SHP (2.52 g/kg/day), Rapa (1.5 mg/kg/day), SM+Rapa and SHP+Rapa. Assessment of anti-fibrotic effects includes clinical signs and body weight, serum biochemistry (AST, ALT, and BUN), histological scoring of liver fibrosis, quantitation of hepatic collagens and α-smooth muscle actin (α-SMA), and zymography for matrix metalloproteinases (MMPs) activity. In clinical signs, Rapa and SM+Rapa group rats revealed remarkable bad appetite, decreased body weight and malnutrition; especially, the mortality of SM+Rapa group was 50%. The contents of AST and ALT in Rapa, Rapa+SM, SHP and Rapa+SHP groups were significantly decreased (P＜0.01, vs CCl4 group). The histopathological examination, scoring of liver fibrosis and determination of hepatic total collagen were significantly reduced in Rapa, Rapa+SM, SHP and Rapa+SHP groups compared to CCl4 group (P＜0.01). α-SMA proteins were markedly reduced in Rapa and Rapa+SM groups (P＜0.001, vs CCl4 group). Decreased MMP-2 activity was noticed in Rapa, Rapa+SM, SHP and Rapa+SHP groups. These results showed anti-fibrotic effects of rapamycin, SM+Rapa, SHP and SHP+Rapa in the rat model of liver fibrosis induced by CCl4. However, the toxity and side effect in Rapa, Rapa+SM were more severe than SHP and Rapa+SHP.

並列關鍵字

liver fibrosis ； traditional Chinese herb ； hepatic stellate cell ； animal model