| ObjectiveTo establish a rat model of hepatic sinusoidal obstruction syndrome（HSOS）,and to explore the effects of resveratrol on rat liver injury induced by monocrotaline（MCT）and its possible mechanisms.MethodsThirty-two male SD rats were randomly divided into the control group,the monocrotaline group and the resveratrol group,with 8 rats in the control group and 12rats in each of two other groups.The experimental group was given monocrotaline 160mg/kg to establish the animal model of hepatic sinusoidal obstruction syndrome.The resveratrol group was given an intraperitoneal injection of 30 mg/kg·d-1resveratrol one day before the gavage;the control group and the monocrotaline group were treated with the solvent in the same way and same dose.Animals were sacrificed 48 hours after gavage,and serum samples and liver tissue were collected.The levels of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,total bilirubin（TBi L）,glutathione（GSH）and malondialdehyde（MDA）in liver tissue were measured,and the histological changes in liver were observed.Changes in liver SIRT1,HIF-1α,VEGF and GPX4 proteins were measured by Western-blot.Results1.After intragastric administration,ALT,AST and TBi L in the monocrotaline group increased（all P<0.01）,the liver tissue pathology showed that hepatocytes were disordered,degeneration,necrosis,hepatic sinusoidal congestion and expansion,central vein endothelial injury,decreased SIRT1 protein expression（P<0.01）,and increased HIF-1αand VEGF protein expression levels（all P<0.01）.After intervention with resveratrol,serum ALT,AST and TBi L decreased（P<0.05;P<0.05;P<0.01）,and liver The pathology was improved,the protein expression level of SIRT1 was increased（P<0.01）,and the protein expression of HIF-1αand VEGF was down-regulated（all P<0.01）.2.Compared with the control group,the level of GSH in the liver tissue of the monocrotaline group decreased（P<0.01）,MDA increased（P<0.01）,and the expression of GPX4 decreased（P<0.01）.Compared with the monocrotaline group,liver GSH level in the resveratrol group rats increased（P<0.01）,MDA decreased（P<0.01）,the expression of GPX4 increased（P<0.01）.ConclusionResveratrol can ameliorate monocrotaline-induced HSOS in rats,and its mechanism is related to activation of SIRT1,inhibition of HIF-1α/VEGF signaling pathway,anti-oxidative stress and up-regulating the expression of GPX4. |
