Effect Of Flavonoids From Astragalus Complanatus On Anti-alcoholic Hepatic Fibrosis In Rats

Objective：To research the effects of flavonoids of Astragalus complanatus（FAC）on alcoholic hepatic fibrosis and and reveal its pharmacological mechanism.Materials and methods：（1）FAC（30,60,120mg/kg）was treated by gactric gavageonce daily in alcoholic hepatic fibrosis rats. Alanine aminotransferase（ALT）and Aspartateaminotransferase（AST）were detected by Reitman-Frankel method; hydroxyproline（Hyp）in hepatic tissues was tested by alkali hydrolysis; hyaluronic acid（HA）, laminin（LN）,procollagen type Ⅰ（PC-Ⅰ）, procollagen type Ⅲ（PC-Ⅲ）, procollagen type Ⅳ（PC-Ⅳ）, and transforming growth factor-β1（TGF-β1）in serum were detected by ELISAkits;alpha-smooth muscle actin（α-SMA）protein content was evaluated using Western blot.（2）To establish activated rat hepatic stellate cells（HSCs-T6）models, including alcohol model,lipopolysaccharide（LPS）model, TGF-β1model, platelet derived growth factor（PDGF）model. The proliferation of HSCs-T6in each model was detected by MTT; HA, LN, PC-Ⅲand TGF-β1were detected to evaluated the functions of HSCs; Smad3, Phospho-Smad3（P-Smad3）, and Smad7were tested to discuss the signal transduction pathway ofTGF-β1.Results：（1）In alcoholic hepatic fibrosis rats, FAC significantly decreased thecontents of ALT、AST、Hyp、HA、LN、PC-Ⅰ、PC-Ⅲ、PC-Ⅳ、TGF-β1and α-SMA（P＜0.01）（.2）FAC had no obvious effect on HSCs-T6proliferation in the quiescent state.But in activated HSCs-T6models FAC dramatically inhibited the cells proliferation（P＜0.01）, decreased the contents of HA, LN, PC-Ⅲ（P＜0.01）, and reduced the secretion ofTGF-β（1P＜0.05or P＜0.01）. Moreover, FAC down-regulated the expression of P-Smad3protein, and up-regulated the synthesis of Smad7protein in HSCs-T6activated by TGF-β1. Conclusions：FAC could alleviate the degree of hepatic damage and fibrosis inducedby alcohol, the mechanism might be related to the inhibition of HSCs activation and thesecretion of TGF-β1.