首页|Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPARγ and NF-κB
Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPARγ and NF-κB
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AIM:To investigate the effects of heme oxygenase (HO)-1 on liver fibrosis and the expression of peroxisome proliferator-activated receptor gamma (PPARγ)and nuclear factor-kappa B (NF-κB) in rats.METHODS:Sixty Wistar rats were used to construct liver fibrosis models and were randomly divided into 5 groups:group A (normal,untreated),group B (model for 4 wk,untreated),group C (model for 6 wk,untreated),group D [model for 6 wk,treated with zinc protoporphyrin Ⅸ (ZnPP-Ⅸ) from week 4 to week 6],group E (model for 6 wk,treated with hemin from week 4 to week 6).Next,liver injury was assessed by measuring serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) and albumin levels.The degree of hepatic fibrosis was evaluated by measuring serum hyaluronate acid (HA),type Ⅳ collagen (IV-C) and by histological examination.Hydroxyproline (Hyp) content in the liver homogenate was determined.The expression levels of alpha-smooth muscle actin (α-SMA) in liver tissue were measured by real-time quantitative polymerase chain reaction (RT-PCR).The expression levels of PPARγ,and NF-KB were determined by RT-PCR and Western blotting.RESULTS:The expression of HO-1 increased with the development of fibrosis.Induction of HO-1 by hemin significantly attenuated the severity of liver injury and the levels of liver fibrosis as compared with inhibition of HO-1 by ZnPP-Ⅸ.The concentrations of serum ALT,AST,HA and IV-C in group E decreased compared with group C and group D (P < 0.01).Amount of Hyp and α-SMA in the liver tissues in group E decreased compared with group C (0.62 ± 0.14 vs 0.84 ± 0.07,1.42 ±0.17 vs 1.84 ± 0.17,respectively,P < 0.01) and group D (0.62-0.14 vs 1.11 ± 0.16,1.42 ± 0.17 vs 2.56 ±0.37,respectively,P < 0.01).The expression of PPARγ at levels of transcription and translation decreased with the development of fibrosis especially in group D; and it increased in group E compared with groups C and D (0.88 ± 0.15 vs 0.56 ± 0.19,0.88 ± 0.15 vs 0.41 ±0.11,respectively,P < 0.01).The expression of NF-κB increased with the development of fibrosis especially in group D; and it decreased in group E compared with groups C and D (1.43 ± 0.31 vs 1.89 ± 0.29,1.43 ± 0.31vs 2.53 ± 0.54,respectively,P < 0.01).CONCLUSION:Our data demonstrate a potential mechanism that HO-1 can prevent liver fibrosis by enhancing the expression of PPARγ,and decreasing the expression of NF-κB in liver tissues.
Heme oxygenase-1Peroxisome proliferator-activated receptor gammaNuclear factor-kappa BLiver fibrosisHemin