Effect of Danshao Huaxian capsule on Gremlin and bone morphogenetic protein-7 expression in hepatic fibrosis in rats

AIM: To observe the effect of Danshao Huaxian capsule (DHC) on the expression of Gremlin and bone morphogenetic protein-7 (BMP-7) in the liver of hepatic fibrosis rats.

AIM:To observe the effect of Danshao Huaxian capsule(DHC)on the expression of Gremlin and bone morphogenetic protein-7(BMP-7)in the liver of hepatic fibrosis rats.METHODS:A total of 75 male Wistar rats were randomly divided into a normal control group(A),a CCl4-induced hepatic fibrosis model group(B),a natural recovery group(C),a low-dose DHC-treated group(D),and a high-dose DHC-treated group(E),with 15 rats in each group.Liver fibrosis was induced by subcutaneous injections of carbon tetrachloride(CCl4)and a highlipid/low-protein diet for 8 wk,except for the rats in group A.Then,the rats in the two DHC-treated groups were administered 0.5 and 1.0 g/kg DHC by gastrogavage once per day for 8 successive weeks,respectively.By the end of the experiment,the level of transforming growth factorβ1(TGF-β1)in the liver homogenate was determined by an enzyme-linked immunosorbent assay.The mRNA and protein expression of Gremlin and BMP-7 in the liver tissue was determined by reversetranscription polymerase chain reaction,an immunohistochemical assay,and Western blot analysis.RESULTS:Compared with group A,the level of TGF-β1and the mRNA and protein expression of Gremlin were significantly higher in group B(TGF-β1:736.30±24.40μg/g vs 284.20±18.32μg/g,P<0.01;mRNA of Gremlin:80.40±5.46 vs 49.83±4.20,P<0.01;positive protein expression rate of Gremlin:38.46%±1.70%vs 3.83%±0.88%,P<0.01;relative protein expression of Gremlin:2.81±0.24 vs 0.24±0.06,P<0.01),and the mRNA and protein expression of BMP-7was significantly lower in group B(mRNA:54.00±4.34vs 93.99±7.03,P<0.01;positive protein expression rate:28.97%±3.14%vs 58.29%±6.02,P<0.01;relative protein expression:0.48±0.31 vs 1.05±0.12,P<0.01).Compared with groups B and C,the degree of hepatic fibrosis was significantly improved,and the level of TGF-β1 and the mRNA and protein expression of Gremlin were significantly lowered in the two DHCtreated groups(TGF-β1:523.14±21.29μg/g,441.86±23.18μg/g vs 736.30±24.40μg/g,651.13±15.75μg/g,P<0.01;mRNA of Gremlin:64.86±2.83,55.82±5.39 vs 80.40±5.46,70.37±4.01,P<0.01;positive protein expression rate of Gremlin:20.78%±1.60%,17.43%±2.02%vs 38.46%±1.70%,29.50%±2.64%,P<0.01;relative protein expression of Gremlin:1.95±0.26,1.65±0.20 vs 2.81±0.24,2.22±0.63,P<0.01),and the mRNA and protein expression of BMP-7 was higher in the two DHC-treated groups(mRNA:73.52±4.56,81.78±5.38 vs 54.00±4.34,62.28±4.51,P<0.01;positive protein expression rate:41.44%±4.77%,47.49%±4.59%vs28.97%±3.14%,35.85%±3.50%,P<0.01;relative protein expression:0.71±0.06,0.81±0.07 vs 0.48±CONCLUSION:The therapeutic mechanism of DHC forhepatic fibrosis in rats may be associated with inhibitionof the expression of Gremlin and up-regulation of the expression of BMP-7.