[Effect of recombinant human augmenter of liver regeneration on gene expression of tissue inhibitor of metalloproteinase-1 in rat with experimental liver fibrosis].

OBJECTIVE

To investigate the influence of recombinant human augmenter of liver regeneration (hALR) on gene expression of tissue inhibitor of metalloproteinase-1 (TIMP1) in rat with experimental liver fibrosis.

METHODS

Carbon tetrachloride was injected into the peritoneal cavities of 150 rats twice a week for 8 weeks. Albumin sensitization and caudal vein attack were conducted to another 136 rats for the duration of 3.5 months, so as to establish two kinds of animal model of experimental liver fibrosis. Recombinant hALR at different doses was given during the process of model making. Specimens of liver were taken at different time-points, then the total RNA of liver tissues was isolated and TIMP1 gene expression levels were measured by reverse transcription polymerase chain reaction.

RESULTS

In both rat models, TIMP(1) gene expression levels increased gradually during the process of model making. The TIMP(1) gene expression level in CCl4 model treated with low dose hALR was 0.86 +/- 0.13, 1.77 +/- 0.23, 2.78 +/- 0.36, and 3.76 +/- 0.50 respectively 2, 4, 6, and 8 weeks after the beginning of model making, all lower than those in the model group, however, without significant difference. The TIMP(1) gene expression level in CCl4 model treated with high dose hALR was 0.63 +/- 0.10, 1.18 +/- 0.20, 1.89 +/- 0.30, 2.63 +/- 0.33 respectively 2, 4, 6, and 8 weeks after the beginning of model making, significantly lower than those in CCl4 model treated with low dose hALR. In the albumin model group the TIMP(1) gene expression level showed no change during albumin sensitization, significantly increased during caudal vein attack, and reached the peak after medel making. The TIMP(1) gene expression level was lower in albumin model treated with low dose hALR during and after caudal vein attack than in the model group and negative control group, however, without significant difference (both P > 0.05). The TIMP(1) gene expression level in albumin model treated with high dose hALR was 2.33 +/- 0.36 and 4.02 +/- 0.53 during and after caudal vein attack respectively, significantly lower than those in CCl4 model group (0.99 +/- 0.14, 2.03 +/- 0.30, 2.99 +/- 0.43, and 4.13 +/- 0.44 respectively 2, 4, 6, and 8 weeks after beginning of model making respectively) and those in albumin model without hALR treatment and that with low dose hALR (4.13 +/- 0.60 and 5.99 +/- 0.83, and 3.70 +/- 0.82 and 5.63 +/- 0.89 during and after caudal vein attack respectively), and negative control group.

CONCLUSION

High dose recombinant human augmenter of liver regeneration is effective in inhibiting gene expression of TIMP(1) in experimental liver fibrosis.