OBJECTIVETo explore the mechanism of action of tanshinone II A for liver protection in hepatic fibrotic mice by observing its effects on signaling pathway of insulin-like growth factor binding protein 7 (IGFBP7) and TGFbeta1/Smad3.

METHODSHepatic fibrosis model was induced by intraperitoneal injection of thioacetamide (TAA). Thirty-six male Kunming mice were divided into five groups: the normal control group (N), the 4-week model group (A), the 4-week tanshinone II A prevented group (B), the 6-week model group (C) and the 3-week tanshinone II A treated group (D). Changes of serum levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), histopathology of liver (HE staining), area density of collagen in liver (Masson staining), expressions of alpha-smooth muscle actin (alpha-SMA), collagen I , fibronectin (FN), transforming growth factor-beta1 (TGF-beta1), Smad3 and IGFBP7 in liver (by immunohiStochemistry), liver content of FN, Smad3 and IGFBP7 (by Western blot), and the hepatocyte apoptosis (by TUNEL) were observed.

RESULTSThe serum levels of ALT and LDH, the expressions of alpha-SMA, collagen I , TGF-beta1 in liver, expressions and contents of FN, Smad3 and IGFBP7 in liver were significantly lower; the liver damage and the hepatic apoptosis index were lesser in Group B than in Group A, also in Group D than in Group C, respectively, all showing statistical significance (P < 0.05).

CONCLUSIONTanshinone II A could improve liver function, inhibit the activation of hepatic stellate cells, reduce the production of extracellular matrix, and protect the hepatocytes, and its of mechanisms of actions might be related with blocking TGF-beta1/Smad3 signaling pathway and down-regulating the expression of IGFBP7 in liver.