基质金属蛋白酶9对大鼠肝脏缺血再灌注后caspase-3表达的影响

The effect of matrix metalloproteinase-9 on the expression of caspase-3 in hepatic ischemic reperfusion injury

目的:探讨基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)对SD大鼠肝脏缺血再灌注后caspase-3表达的影响及其可能的机制。方法:建立雄性SD大鼠70%肝脏缺血再灌注损伤模型。将48只大鼠随机分为3组(n=16):假手术组(S组),缺血再灌注组(I/R组)和强力霉素处理组(DC组)。再灌注3 h后检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肿瘤坏死因子-α(TNF-α)、肝组织丙二醛(MDA)含量。通过免疫组化方法检测肝脏组织中MMP-9及caspase-3的表达情况。结果:肝脏缺血再灌注后,IR组的ALT、AST、TNF-α、MDA的阳性表达率明显高于S组(P<0.05),而DC组中各指标得到改善。在I/R组中,MMP-9及caspase-3较S组表达增强,而在DC组中其表达较I/R组减弱。结论:MMP-9的低表达,可减轻炎症细胞及因子的释放和浸润,抑制caspase-3介导的肝脏细胞的凋亡。

Objective：To investigate the effect of matrix metalloproteinase-9 on the expression of caspase-3 and its possible mechanisms.Methods：The model of 70% hepatic ischemia-reperfusion was established in SD male rat.Total 48 SD rats were randomly divided into three groups（n = 16）： sham operation group（S group）,ischemia-reperfusion group（I/R group） and doxycycline treated group（DC group）.After 3 hours of reperfusion,the enzyme levels in serum were examined,including ALT,AST,TNF-α and MDA.The expressions of MMP-9 and Caspase-3 were determined in immunohistochemistry.Results：After ischemia-reperfusion,the levels of ALT,AST,TNF-α and MDA expression in I/R group was significantly higher than those in S group.After treatment of oral doxycycline,the all above abnormal parameters were retrieved remarkably（P 〈 0.05）.In the I/R group,MMP-9 and caspase-3 expressions increased,comparing with that in S group,while its expression decreased in the DC group,comparing with that in I/R group.Conclusion：The low expression of MMP-9 reduces the release and infiltration of inflammatory cells,inhibits caspase-3-mediated apoptosis of liver cells.