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Ischemia/reperfusion (I/R) and portal hypertension have been implicated in small‐for‐size liver graft dysfunction. Matrix metalloproteinases‐2 and ‐9 (MMP‐2/9) are critically proposed to involve in hepatic I/R injury and activated by hemodynamic force. We hypothesized that MMP‐2/9 overexpression played a crucial role in acute graft injury following small‐for‐size liver transplantation (LT). Rats were randomly assigned into four groups: 75% partial hepatectomy (PH); 100% LT; 25% LT and 25% LT treated with CTT peptide (MMP‐2/9 inhibitor). ELISA, real‐time PCR, gelatin zymography and immunohistochemistry were used to determine the expression pattern of MMP‐2/9 in liver tissue. MMP‐9 expression was significantly increased 6 h after reperfusion and reached a peak 12 h in the 25% LT group, whereas MMP‐2 was expressed in all groups invariably. Compared with the 25% LT group, rats from CTT‐treated group exhibited markedly decreased alanine aminotransferase and total bilirubin values, downregulated proinflammatory cytokines, attenuated malondialdehyde (MDA) and myeloperoxidase (MPO) activities, and improved liver histology. Likewise, MMP‐9 inhibition significantly reduced number of TUNEL‐positive cells and caspase‐3 activity, along with decreased protein levels of Fas and Fas‐L. Specifically, rat survival was also improved in the CTT‐treated group. These results support critical function of MMP‐9 involved in acute small‐for‐size livergraft injury....
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