Plasma-kallikrein clearance during liver regeneration after partial hepatectomy in the rat

Aims/Background. The liver clears circulating plasma-kallikrein through a r eceptor-mediated endocytosis process: an initial fast phase is followed by a slow exponential phase. Methods: To determine whether the clearance rate of plasma-kallikrein is affected during liver regeneration, we perfused iso lated rat livers with rat plasma-kallikrein (rPK) at 0, 1, 2, 3 and 7 days after partial hepatectomy or sham operation. Results. Liver regeneration wa s followed by the expression of the proliferating-cell nuclear antigen (PCN A) labeling index. The serum concentration of alpha(2)-macroglobulin, an ac ute phase protein in rats, was measured. At day 1, the fast phase of rPK cl earance rate increased in hepatectomized rats when compared with day 0 (4.9 +/-0.4 and 3.7+/-0.4 mU/g liver min, p<0.05). However, at day 2, the rPK fa st phase clearance rate dropped significantly (2.6+/-0.2, p<0.05), when com pared with day 1. No difference was found among the sham groups at differen t days of hepatectomy. These changes seem to be independent of the acute ph ase reaction. The regenerative liver weight increased continuously during t he observation period. PCNA expression increased significantly after hepate ctomy, with maximal PCNA-labeling indices at days 1 and 2, declining therea fter. Conclusion. The rPK fast phase clearance rate changes during liver re generation, with a zenith occurring when PCNA labeling index is maximal (da y 1) and a nadir occurring at the mitotic phase (day 2).