MMP2/9 downregulation is responsible for hepatic function recovery in cirrhotic rats following associating liver partition and portal vein ligation for staged hepatectomy.

Abstract

BackgroundAssociating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was introduced in 2007. The current study explored the mechanisms of rapid liver hypertrophy after ALPPS in cirrhotic rats.MethodsA cirrhotic rat model was constructed and portal vein ligation (PVL) or ALPPS treatments were administered. The liver hyperplasia rate of the rats was calculated, and hepatic function was evaluated using biochemical factors and the indocyanine green excretion test. Subsequently, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and hematoxylin and eosin (HE) staining were performed to determine the degree of liver regeneration. Differentially expressed genes during the rapid liver hypertrophy were detected by bioinformatics analysis, followed verification using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry.ResultsThe body weight of rats that underwent PVL and ALPPS changed during the first 1–4 days postoperatively, and the alterations were more pronounced in rats receiving ALPPS. The recovery of body weight in cirrhotic rats was slower than that in normal rats. The levels of biochemical factors and the indocyanine green retention rate increased 1 day after PVL and ALPPS, and then decreased gradually. PVL and ALPPS elevated the levels of cytokines, inflammatory factors, and proliferating cell nuclear antigen (PCNA) in rats at 1 day postoperatively. HE observation of rat liver condition showed that rats recovered faster within the first 4 days postoperatively. ALPPS surgery resulted in a significant downregulation of matrix metalloproteinase (MMP)2/9 expression in cirrhotic rats at postoperative day 4.ConclusionsLiver function was partially recovered in cirrhotic rats after ALPPS, and the underlying mechanisms may involve PCNA and MMP2/9.