Oral therapy of recombinant Subtilisin QK-2 potentiates thrombolytic
effect in a carrageenan-induced thrombosis animal model
Subtilisin QK is a nattokinase-like serine protease which demonstrates
high efficiency for direct cross-linked fibrin degradation, without
activation of plasminogen. It was resistant capacity against the
digestion of mimics pancreatic enzyme and could be absorbed throughout
ex vivo intestine with fibrinolytic activity in a time-dependent manner.
The result of bioluminescence image using nude mice also proved that
rSubtilisin QK could infiltrate into all organs from intestinal mucosa.
Since rSubtilisin QK could also elevated the levels of plasma levels of
fibrin/fibrinogen degradation products and D-dimer (they are sensitive
indicators of in vivo fibrinolytic activity) in rats, its prevention
effect was investigated in κ-carrageenan-induced rat model. Thrombosis
rats were oral treated with rSubtilisin QK for 7 days, and the length of
tail-thrombosis was then measured. Compared to control group, the
average length of tail-thrombosiswere reduced and the vessel cross
section of ears and tails occupied by thrombosis was relieved among the
thrombosis rats treated with rSubtilisin QK. Furthermore, the levels of
tissue plasminogen activator were increased in cultured HUVECs
stimulated with rSubtilisin QK, while plasminogen activator inhibitor-1
showed the opposite trend simultaneously, suggesting the activation of
plasminogen. In conclusion, rSubtilisin QK exerted thrombolytic effects
in vivo and may be a potential oral thrombolytic agent.