Hepatic ischemia/reperfusion promote hematogenic metastasis of hepatocellular carcinoma in mice through induction of MMP-9 expression / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the effect of ischemia/reperfusion(I/R) on tumor metastasis in a experimental mouse model of hematogenous metastasis after I/R; we also quantitated expression of matrix metalloproteinases-9 (MMP-9) during I/R.Methods An experimental mouse model of metastasis after partial hepatic I/R was designed to determine the effects of I/R on tumor metastasis to liver.Tumor loads were valued 7 days after operation.In addition,tissue analysis for alanine transaminase,aspartate transaminase (AST) and matrix metalloproteinases and 8 h reperfusion were performed.Results After 2 h hepatic reperfusion,ALT and AST in I 45 min group were higher than the sham group and I 30 min group (P ＜0.05).ALT and AST in the sham group were both a little higher than the normal.ALT and AST in the I 45 min group and I 30 min group at 8 h were both higher than those at 2 h reperfusion(P ＜0.05).The tumor load (valued by Hepatic replacement area) and the expression of MMP-9 in ischemic lobe in I 45 min group were greater than that after 30 min group and sham group.(P =0.013,P =0.007).There was no statistical difference on tumor load between the right lobe of sham operated mice and the right lobe (non-ischemic lobe) of mice subjected to I/R(P =0.089).Mouse survival were compared among the groups.Mice in Sham group lived longer than I 30 min group (P =0.041).And there were no statistical significance between I 45 min group and I 30 min group (P =0.055).MMP-9 expression in I 45 min group was higher than I 30 min group(P ＜ 0.001).Conclusion Hepatic I/R promotes liver hematogenic metastasis of hepatocellular carcinoma in mice through induction of MMP-9 expression.