Mechanism of ligustrazine retards hepatic fibrosis via TGF-β/Smad channelin biliary atresia
Objective To investigate the mechanism of tanshinone ⅡA delaying hepatic fibrosis in biliary atresia by regulating SMAD4 and SMAD7 proteins.Methods Thirty male SD rats were divided into the normal group,sham operation group,model group,pirfeni-done group(300 mg/kg)and tanshinone ⅡA group(20 mg/kg)according to random number table,with six rats in each group.In addition to the normal group and sham operation group,the other groups of rats were injected with anhydrous ethanol in the common bile duct to replicate the biliary atresia liver fibrosis model.On the first day after modeling,the rats in the pirfenidone group and tanshinone ⅡA group were given corre-sponding drugs,and the rats in the sham operation group and model group were given equal volume normal saline(10 mL/kg).After 20 days of administration,specimens were taken from animals overanesthetized with pentobarbital sodium,biochemical indexes and histopathological changes of liver were compared.Serum alanine aminotransferase,aspartate aminotransferase and total bilirubin levels were detected.Western blot analysis was performed to detect the expression of SMAD4 and SMAD7 and collagen Ⅰ in liver tissue.Results Compared with normal group,serum alanine aminotransferase,aspartate aminotransferase and total bilirubin in model group were increased(P<0.05),liver tissue showed obvious fibrosis changes,collagen Ⅰ and SMAD4 expression were increased,and SMAD7 expression was decreased(P<0.05).However,the expressions of SMAD4 and collagen Ⅰ in the pirfenidone group and tanshinone ⅡA group decreased,while the expression of SMAD7 in-creased(P<0.05),and tanshinone ⅡA group had obvious advantages in improving liver fibrosis compared with pirfenidone group.Conclu-sions Tanshinone ⅡA can effectively delay the progression of liver fibrosis in biliary atresia,possibly by regulating the expression of key pro-teins SMAD4 and SMAD7 in TGF-β/Smads,thereby reducing the deposition of collagen Ⅰ in liver tissue.
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