The effect of pirinixic acid on the expressions of PPAR-α,NF-κb and MMP-9 in paracancerous liver tissues after transarterial embolization of liver cancer

Objective: To investigate the effects of pirinixic acid (WY14643) on the expressions of peroxisome proliferators-activated receptor-α (PPAR-α), nuclear factor-κb (NF-κb) and matrix metalloprotein-9 (MMP-9) in paracancerous liver tissues after transarterial embolization (TAE) of liver cancer. Methods: The rabbit VX2 liver cancer model was established, the implantation and growth of tumor were followed up. A total of 60 successful modeling rabbits were randomly and equally divided into 3 groups with 20 rabbits in each group. The rabbits of control group received no treatment, and the rabbits of TAE group received TAE only. For the rabbits of combination treatment group, continuous injection of WY14643 was adopted for three days which was followed by TAE. The serum levels of ALT and AST in peripheral blood of experimental rabbits were determined by chemical colorimetry before and after treatment. The mRNA expressions of PPAR-α, NF-κb and MMP-9 in paracancerous liver tissues were tested by fluorescence quantitative polymerase chain reaction. Immunohistochemistry was used to detect the protein expressions of PPAR-α, NF-κb and MMP-9 in paracancerous liver tissues. Results: There were no statistically significant differences in preope rative ALT and AST levels between each other among the three groups. The postoperative levels of ALT and AST in the combination treatment group were higher than those in the control group, while lower than those in the TAE group, the differences were statistically significant. The expression of PPAR-α mRNA in the paracancerous liver tissues in the combination treatment group was significantly higher than that in the TAE group and in the control group, the difference was statistically significant. The expression levels of NF-κb mRNA and MMP-9 mRNA in the paracancerous liver tissues in the combination treatment group were significantly lower than those in the TAE group, the differences were statistically significant, but when compared with those in the control group the differences were not statistically significant. The positive rate of PPAR-α protein in the paracancerous liver tissues in the combination treatment group was 70%, which was obviously higher than 30% in the control group and than 20% in the TAE group. The positive rates of NF-κb and MMP-9 protein in the combination treatment group were 30% and 35% respectively, which were significantly lower than 65% and 75% respectively in the TAE group but were not significantly different with 20% and 25% respectively in the control group. Conclusion: Pirinixic acid can alleviate the inflammatory reaction of paracancerous liver tissues and the damage of liver function after TAE, which may be related to its functions of promoting PPAR-α expression and inhibiting NF-κB signaling pathway and downstream MMP-9 expression. (authors)