title: Systemic administration of argatroban inhibits protease-activated receptor-1 expression in perihematomal tissue in rats with intracerebral hemorrhage.
abstract: 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 (0.9mg/kg) after models were established for 3h and 12h, intraperitoneally. All rats were killed to harvest brains after models were established for 24h. 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.
authors.affiliation: Department of Neurology, General Hospital of Shenyang Military Command, Shenyang, China.
authors.forename: Zhong-He
authors.initials: ZH
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Qu
authors.forename: Chao-Dong
authors.initials: CD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D015153:Blotting, Western; D001834:Body Water / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D001929:Brain Edema / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000378:metabolism*; D005260:Female; D008297:Male; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D044463:Receptor, PAR-1 / Q000096:biosynthesis*; D013238:Stereotaxic Techniques; D013449:Sulfonamides
chemical_list: D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D044463:Receptor, PAR-1; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban