Effect of Anluohuaxianwan on the expression of matrix metalloproteinases and their inhibitors in rat liver with fibrosis / 中华肝脏病杂志

ABSTRACT

Objective@#To investigate the effect of anluohuaxianwan (ALHXW) using rat model of carbon tetrachloride (CCl4) induced liver fibrosis on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).@*Methods@#Thirty-six male Wistar rats were randomly assigned into control, model and treatment groups. Rats in the model and treatment groups were injected intraperitoneally with 40% CCl4 (2 ml/kg), and the control group were given isotonic saline twice a week for six weeks. Meanwhile, the treatment group were gavaged with ALHXW solution daily (concentration 0.15 g/ml, 9.9 ml/kg) for 6 weeks, while the control and model groups were given isotonic saline once a day for 6 weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at the end of third and sixth week. At the end of six weeks, liver tissues were harvested for histopathological evaluation and the detection of mRNA and protein expression levels of MMP-2/13 and TIMP-1/2. According to different data, LSD method, parametric (one-way ANOVA) and non-parametric tests (Kruskal-Wallis H-test and Mann-Whitney U test) were used for statistical analysis.@*Results@#Compared with the model group, ALHXW markedly alleviated liver injury in the treatment group, and thereby improved the general state of rats, liver and spleen morphological characteristics, and ALT and AST levels. Histopathological examination demonstrated that the extent of liver fibrosis was improved (2.75 ± 0.75 vs. 3.55 ± 0.69, P = 0.015) in the treatment group as compared with the model group. The mRNA and protein expression levels of MMP-13 in the treatment group were significantly higher than that of the model group (mRNA 10.50 ± 7.64 vs. 4.40 ± 2.97, P = 0.029. Protein 1.15 ± 0.09 vs. 0.78 ± 0.21, P = 0.016), whereas the mRNA and protein expression levels of MMP-2, TIMP-1/2 in the treatment group were significantly lower than that of the model group (mRNA 4.55 ± 3.29 vs. 7.83 ± 4.19, P = 0.048; 1.66 ± 0.73 vs. 3.69 ± 2.78, P = 0.023; 2.25 ± 1.16 vs. 3.41 ± 1.51, P = 0.049; respectively. Protein 0.44 ± 0.11 vs. 0.65 ± 0.05, P = 0.03; 0.69 ± 0.06 vs. 1.07 ± 0.21, P = 0.016; 0.46 ± 0.09 vs. 0.81 ± 0.13, P = 0.003; respectively).@*Conclusion@#ALHXW exerts anti-liver fibrosis effects mainly by improving liver function, inhibiting the activation of hepatic stellate cells, enhancing the expression of MMP-13, and inhibiting the expression of MMP-2 and TIMP-1/2.