摘要
目的 观察基质金属蛋白酶-9（MMP-9）在小鼠肝脏部分缺血再灌注并肝癌细胞门静脉转移模型中的作用.方法 建立小鼠肝脏部分缺血再灌注并肝癌细胞门静脉转移模型.建模后14天观察各组肝脏肿瘤生长情况.生化法、明胶酶谱和实时定量PCR法检测肝酶和基质金属蛋白酶等的表达情况.结果 肝脏缺血再灌注2h后,缺血45 min组和缺血30 min组的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平显著高于假手术组（P＜0.05）,缺血45 min组ALT和AST水平显著高于缺血30 min组（P＜0.05）.假手术组术后ALT和AST均一过性轻度升高.再灌注8h时,缺血45 min组和缺血30 min组ALT和AST水平高于2h时（P＜0.05）;术后7天缺血45 min组左肝叶肿瘤负荷较缺血30 min组和假手术组高（P=0.013,P=0.007）,但假手术组右肝叶（无缺血肝叶）肿瘤负荷与缺血30 min组右肝叶相比差异无统计学意义（P =0.089）.缺血30 min组生存时间少于假手术组,差异有统计学意义（P=0.041）,缺血30 min组与缺血45 min组两者生存时间差异无统计学意义（P =0.055）.缺血45 min组MMP-9水平高于缺血30 min组（P＜0.001）,相应基因表达水平亦呈相似变化.结论 肝脏缺血再灌注可促进肝癌细胞门静脉转移,部分机制可能是通过上调MMP-9的表达实现的.
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.
出处
《中华肝胆外科杂志》
CAS
CSCD
北大核心
2014年第11期810-815,共6页
Chinese Journal of Hepatobiliary Surgery
基金
中国博士后科学基金（2009045513）
关键词
肝癌
缺血再灌注
基质金属蛋白酶-9
门静脉转移
Hepatocellular carcinoma
Ischemia/reperfusion
Matrix metalloproteinase-9
Portal vein metastasis
