Systemic administration of argatroban inhibits protease-activated receptor-1 expression in perihematomal tissue in rats with intracerebral hemorrhage

The present study investigated the role of thrombin in the expression of protease-activated receptor-1 (PAR-1), and the effect of argatroban (Arg) a direct thrombin inhibitor, on PAR-1 expression in perihematomal tissue with intracerebral hemorrhage (ICH). For these experiments 90 rats were divided into 5 groups: sham, ICH, argatroban-treated ICH (ICH + Arg), thrombin (TM) and argatroban-treated thrombin (TM + Arg). The ICH model or thrombin injection models were established by injecting autologous blood or thrombin, respectively. Rats in TM + Arg and ICH + Arg groups were administered argatroban (0.9 mg/kg) after models were established for 3 h and 12 h, intraperitoneally. All rats were killed to harvest brains after models were established for 24 h. The levels of PAR-1 protein and PAR-1 mRNA expression were detected by Western blot and RT-PCR, respectively. Brain water content was also measured. Our results showed that the levels of PAR-1 protein or PAR-1 mRNA in ICH and TM groups were up-regulated compared to that observed for the sham group; while the levels observed in ICH + Arg group and TM + Arg group were significantly lower than that observed for the ICH group and TM group (P < 0.01 or P < 0.05). The intraperitoneal administration argatroban also significantly reduced edema in ICH or TM group (P < 0.05). Our observations suggested that the production of thrombin following ICH play a key role in the up-regulation of PAR-1 and anti-PAR-1 by systemic administration of argatroban, and may be a potential strategy for ICH therapy. (C) 2011 Elsevier Inc. All rights reserved.