CAJ | 학술논문

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.
목적 관찰기질금속단백매-9(MMP-9)재소서간장부분결혈재관주병간암세포문정맥전이모형중적작용.방법 건립소서간장부분결혈재관주병간암세포문정맥전이모형.건모후14천관찰각조간장종류생장정황.생화법、명효매보화실시정량PCR법검측간매화기질금속단백매등적표체정황.결과 간장결혈재관주2h후,결혈45 min조화결혈30 min조적병안산안기전이매(ALT)、천동안산안기전이매(AST)수평현저고우가수술조(P＜0.05),결혈45 min조ALT화AST수평현저고우결혈30 min조(P＜0.05).가수술조술후ALT화AST균일과성경도승고.재관주8h시,결혈45 min조화결혈30 min조ALT화AST수평고우2h시(P＜0.05);술후7천결혈45 min조좌간협종류부하교결혈30 min조화가수술조고(P=0.013,P=0.007),단가수술조우간협(무결혈간협)종류부하여결혈30 min조우간협상비차이무통계학의의(P =0.089).결혈30 min조생존시간소우가수술조,차이유통계학의의(P=0.041),결혈30 min조여결혈45 min조량자생존시간차이무통계학의의(P =0.055).결혈45 min조MMP-9수평고우결혈30 min조(P＜0.001),상응기인표체수평역정상사변화.결론 간장결혈재관주가촉진간암세포문정맥전이,부분궤제가능시통과상조MMP-9적표체실현적.
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.