Alterations in protease nexin-1, thrombin and protease-activated receptor-1 expressions after intracerebral hemorrhage in rats

Abstract

Objective To investigate the changes in the expressions ofprotease nexin-1(PN-1), thrombin and protease-activated receptor-1 (PAR-1) in the brain tissue of rats after experimental intracerebral hemorrhage (ICH). Methods Experimental ICH was induced in adult rats by stereotactic injection of autologous blood into the left caudate nucleus. The expression levels of PN-1, thrombin and PAR-1 proteins in the sham-operated group and experimental ICH group were detected at 3, 6, 10, 12, 24, 48 and120 h after the operation using Western blotting. Results A low level of PN-1, thrombinand PAR-1 expressions was detected in the brain tissues of the sham-operated rats. In the ICH group, PN-1 protein increased at 3 h after ICH and peaked at 10 h with subsequent gradual declination;the expression ofthrombin protein increased significantly at 12 h after ICH and reached the peak level at 48 h;PAR-1 increased significantly at 3 h after ICH, peaked at 48 h, and maintained the high level till 120 h. The expression levels of PN-1, thrombin and PAR-1 proteins in the brain tissues showed significant differences between the ICH group and sham-operated group (P<0.05). Inverse correlations were found between PN-1 and PAR-1 at 10 h afterICH (r=-0.900, P<0.05) and between PN-1 and thrombin at 12 and 120 h (r=-0.900 and -0.895, respectively, P<0.05). Conclusion The up-regulation ofthrombin mediates neurotoxic injuries after ICH by continuously activating PAR-1 in rat brain tissues, and the concurrent increment of PN-1 expression may inhibit the toxic effects of thrombin overexpression. The increased expressions of PN-1, thrombin and PAR-1 might be associated with the pathogenesis of neural injuries following ICH. Key words: Intracerebral hemorrhage; Protease nexin-1; Thrombin; Protease-acfivated receptor-1