基质金属蛋白酶-9与小体积移植肝早期损伤的相关性研究  

Correlation between overexpression of matrix metalloproteinase-9 with acute graft injury after small-forsize liver transplantation

作　　者：马震宇[1] 钱建民[1] 崔一尧[1] 王乾伟[1] 汪昉睿[1] 

机构地区：[1]复旦大学华山医院普外科,上海200032

出　　处：《中华器官移植杂志》2010年第7期400-404,共5页Chinese Journal of Organ Transplantation

基　　金：国家十一五支撑计划课题（2008BAI60B03）

摘　　要：目的观察不同体积肝移植术后早期移植肝内基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的表达及活化特点，探讨MMP-2和MMP-9在小体积移植肝早期损伤中的作用机制。方法随机将108只SD大鼠分成3组，每组36只。分别为：全肝（100％肝体积）移植组、半肝（50％肝体积）移植组和小体积肝（25％肝体积）移植组。分别检测移植肝再灌注后0．5、6、12、24、48、72h的肝功能及移植肝组织中丙二醛（MDA）和髓过氧化物酶（MPO）浓度，观察移植肝组织病理学特征，并运用双抗夹心酶联免疫吸附试验（ELISA）、实时定量聚合酶链反应（PCR）、明胶酶谱和免疫组织化学方法检查移植肝中MMP-2和MMP-9的表达情况。结果与全肝和半肝移植组比较，小体积肝移植组再灌注后6-24hMMP-9表达明显升高；而且MMP-9活化和表达增高伴随着移植肝功能损害和严重的缺血再灌注损伤。MMP-9早期表达都集中在移植肝门静脉周围，与门静脉高灌注密切相关。结论MMP-9表达升高是小体积移植肝早期重要的致损伤因素；肝移植术后门静脉高灌注可能是触发MMP-9活化和表达的重要原因。Objective Portal hypertension and isehemia/reperfusion （I/R） have been implicated in small-for-size liver graft dysfunction. Matrix metalloproteinases-2 （MMP-2） and MMP-9 are critically involved in hepatic I/R injury. The goal of this study was to investigate the role of MMP-2 and MMP-9 in acute small-for-size graft injury. Methods 108 rats were divided into three groups： 100% （full-size）, 50 % （half-size） and 25% （quarter-size） liver transplantation groups. Blood and liver samples were collected to assess liver function, hepatic malondialdehyde （MDA） content, tissue myeloperoxidase （MPO） activity and histological changes. ELISA, real-time PCR, gelatin zymography, and immunohistochemistry were used to determine the expression pattern of MMP-2 and MMP-9 in liver grafts. Results The expression levels of MMP-9 were significantly higher in quartersize and half-size grafts than those in full-size liver grafts 6, 12, and 24 h after reperfusion. And the elevated levels of MMP-9 were related to graft size inversely. However, MMP-2 was expressed and remained in all groups invariably. MMP-9 overexpression was accompanied by extensive liver I/R injury, as evidenced by significant increases in hepatic microscopic damage scores, MDA content, MPO activity and liver function levels. Furthermore, MMP-9 was found mainly to locate around periportal area. The presence of the active form of MMP-9 was significantly higher in small-for-size grafts, which was correlated with sinusoidal dilatation, congestion and hemorrhage. Conclusion These results support critical function of MMP-9 in acute small-fovsize liver graft injury. Moreover, portal hypertension may be a crucial trigger for expression and activation of MMP-9.

关 键 词：基质金属蛋白酶-9 肝移植 再灌注损伤 

分 类 号：R657.3[医药卫生—外科学]