Effects Of Rhein In Combination With Tetrathylpyrazine On Experimental Hepatic Fibrosis Induced By Carbon Tetrachloride

OBJECTIVE: To investigate the anti-fibrotic and hepatocyte- protective effects of rhein (RH) in combination with tetramethylpyrazine (TMP), and to elucidate its possible mechanism.METHODS: Fifty male Wistar rats were randomized into five study groups: model contrast group, colchicines-treated group (COL0.2mg /kg), rehin-treated group (RH 100mg/kg), tetramethylpyrazine-treated group (TMP 80mg/kg), and combined two drugs treatment group( RH 25mg/kg + TMP 20mg/kg). All rats were given subcutaneous injection of 50% Carbon tetraiodide three times every weeks. Rats of different treated groups were given different dose drugs by daily gavage for six weeks. At the end of study, all rats were killed, The liver function were assaied by omni-auto biochemical meter. The levels of Malondialdehyde ,Superoxide dismutase and Hydroxyproline in hepatic tissue were determinated by chromatometry. Degrees of fibrosis were detected by histopathology under optical microscopy and electron microscopy. The expressions of Tissue inhibitor of matrix metalloproteinase-1, Von Willebrand factor, and α-Smooth muscle actin were measured by immunochemical techniques. RESULTS: (1)Compared with model contrast group, a combination of two drugs could markedly decreased the levels of Alanine aminotransferase, Aspartate aminotransferase, and was superior to colchicines (P<0.01) and single drug(P<0.01). ⑵ Contrasted with model group, a combination of two drugs could significantly prevent the increase of Malondialdehydeand Hydroxyproline , the decrease of Superoxide dismutase content in hepatic tissue. (P<0.01), and also superior to other groups. ⑶ In contrast to model contrast group, a combination of two drugs could strikingly reduced the degrees fibrosis and the expressions of Tissue inhibitor of matrix metalloproteinase-1, Von Willebrand factor, and α-Smooth muscle actin(P<0.01). furthermore it apparently superior to single drug(P<0.01). ⑷ As compared with model contrast group, a combination of two drugs could notablely decreased the scores of hepatic fibrosis (P<0.01), and also superior to other groups.CONCLUSION: A combination of Rehin and tetramethylpyrazine could improve liver functions and slow down the progression of hepatic fibrosis. The mechanism of such effects may due to: ⑴ the decrease of the content of MDA and Hyp, the increase of SOD; ⑵the reduce of heptocellular apoptosis, degeneration, and necrosis. ⑶the inhibition of HSC activation, proliferation by down-regulation of the expressions of α-SMA ; ⑷ the reduction of collegen systhesis and the increase of ECM by down-regulation of TIMP-1; ⑸the relieve of hepatic sinusoidal capillarization by down-regulation of vWF.