ABSTRACT
Objective To evaluate the efficacy and safety of a novel mutated recombinant tissue-type plas-minogen activator (rt-Pam) in a rat model of acute cerebral thrombosis. Method Eighty-seven adult Wister rats were randomly divided into control group, recombinant tissue-type plasminogen activator (rt-PA) group, low dose of rt-Pam group and routine dose of rt-Pam group. The rats of different groups were treated for 3 hours after thrombosis of middle cerebral artery. The size of infarction, neurological scores and severity of hemorrhage were observed 24 hours after treatment. The protective role of rt-Pam in the brain tissue was evaluated as per the infiltration of neutrophils and the concentration of plasminogen activator receptor-1 (PAR-1). Results Compared with control group, the sizes of infarction in the low dose of rt-Pam group and routine dose of rt-Pam group were significantly smaller [(108.5 ±27.3) mm3 and (68.3 ±17.2) mm3 vs. (323.4 ±42.3) mm3]. The neurological scores were evidently correlated with the size of infarction (r = 0.613, P<0.001), while the liability of cerebral hemorrhage in low dose of rt-Pam group was not significantly increased. The rt-Pam also reduced the production of myeloperox-idase, as well as the production of PAR-1 in comparison with rt-PA group [(13.8 ± 3.1) vs. (28.3±4.5), P <0.00l]. Conclusions The novel rt-Pam could be a better thrombolytic agent than rt-PA in treating acute stroke.