| Hepatic fibrosis could be defined as a wound healing process to a variety of chronic insults. It is characterized as an excessive deposition of extracelluar matrix (ECM). Transforming growth factor-β1 (TGF-β1) plays a critical role in the development of hepatic fibrosis. During the procession of hepatic fibrosis, TGF-β1 can activate hepatic stellate cell (HSC), increase the deposition of ECM, inhibit the degradation of collagenase and matrix metalloproteinases (MMPs), and so on. There is evidence that, TGF-β1 and connective tissue growth factor (CTGF) have some same functions, for example: they can promote the proliferation of fibroblast cell, increase the mRNA expression of procollagen-α1,integrin-α5 and fibronectin. In addition, increasing evidence from in vivo and in vitro models of tissue fibrosis suggest that CTGF may represent a downstream effector molecule of the profibrotic activities of TGF-β1 in the maintenance and repair of connective tissues and within fibrotic disease settings. Litsea corneana levevar, which is distributed in southern part of China, has been widely used as a health promoting tea for several centuries. Previous study has showed that Lissea corneana levevar has hypolipidemic effect in rats fed with high fat diet. It has been identified that flavonoids are the main chemical components in this plant, which possess antioxidant property. The total flavonoids also have effect on alcoholic steatohepatitis and nonalcoholic steatohepatitis.In order to further investigate the protective effect of the total flavonoids of Litsea corneana level (TFLC) on liver, the present study is to explore the effect of TFLC on hepatic fibrosis and its partly mechanisms.The main contents are divided into three sections as follows:1. The effect of TFLC on hepatic fibrosisSD rats randomly divided into six groups (the normal, the model, the TFLC (100, 200,400mg/kg) and the colchicin (0.1mg/kg) groups). The model of hepatic fibrosis is induced by injecting 50% CCl4 (1ml/kg) twice weekly for 12 weeks. Form d7 week, all the therapeutic groups were treated with the TFLC (100,200,400mg/kg) and colchicin (0.1mg/kg) respectively for 6 weeks. Compared with the model group, TFLC (200,400mg/kg) not only reduce the liver index, but also reduce the serum content of ALT, AST, HA, LN, PⅢNP, CⅣ, TGF-β1 and Hyp content in liver. The histopathological analysis suggested that the TFLC (200,400mg/kg) can also reduce the degree of hepatic fibrosis. These results suggest that TFLC has protective effect on hepatic fibrosis.2. The effect of TFLC on expression of TGF-β1/CTGF in liver tissueTFLC (200mg/kg) can decrease the mRNA and protein expression of TGF-β1 and CTGF in liver tissue. These results suggest that TFLC has protective effect on hepatic fibrosis, which might be associated with inhibiting the TGF-β1 and CTGF expression of liver tissue in hepatic fibrosis rats.3. The effect of TFLC on expression of TGF-β1/CTGF in HSC-T6 cellsHSC-T6 cell was used as in vitro model to evaluate the anti-proliferation effect of TFLC. TFLC(0.01,0.1,1,10,100 mg/L) could inhibit the proliferation of HSC-T6 cell. TFLC can also decrease the mRNA and protein expression of TGF-β1 and CTGF in HSC-T6 cell. These results suggest that TFLC can inhibit the proliferation of HSC-T6 cell, so as to reduce the expression of TGF-β1 and CTGF. This might be one of the mechanism of it has effect on hepatic fibrosis. |
