Correlation between overexpression of matrix metalloproteinase-9 with acute graft injury after small-for-size liver transplantation
10.3760/cma.j.issn.0254-1785.2010.07.006
- VernacularTitle: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
- Author:
Zhenyu MA
;
Jianming QIAN
;
Yiyao CUI
;
Qianwei WANG
;
Fangrui WANG
- Publication Type:Journal Article
- Keywords:
Matrix Metalloproteinase 9;
Liver transplantation;
Reperfusion injury
- From:
Chinese Journal of Organ Transplantation
2010;31(7):400-404
- CountryChina
- Language:Chinese
-
Abstract:
Objective Portal hypertension and ischemia/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 quarter-size and half-size grafts than those in full-size liver grafts 6, 12, and 24 h after reperfusioa And theelevated 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-for-size liver graft injury. Moreover,portal hypertension may be a crucial trigger for expression and activation of MMP-9.
