Abstract: AIM: To study the thrombolysis activities of wide type Desmodus rotundus Salivary Plasminogen Activivator (DSPAwt) and its mutations F195 and QNRR expressed in yeast Pichia methanolica. METHODS: The rat model of artery-vein bypass thrombosis was used to measure the thrombolysis activities of DSPA^wt, F195 and QNRR, in which indexes such as weight of thrombus, bleeding time (BT), thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer were investigated. DSPA was expressed in CHO cells (DSPAαl) and the launched thrombolytic drug rt-PA were used as positive controls. RESULTS: Positive controls as well as DSPA^wt, F195 and QNRR at doses of 0.7 mg/kg and 1.5 mg/kg individually showed thrombolysis potency, which decreased the weight of thrombus, delayed the levels of BT, TT, PT, APTT and elevated the level of D-dimer. F195, QNRR and DSPAαl had the similar higher activities, while DSPA^wt possessed limited thrombolysis effects. CONCLUSION: The results suggest a novel method to express DSPAs for further development as a novel type of drug for treatment of thrombotic diseases such as acute ischemic stoke.

Key words: Desmodus rotundus, Thrombolysis activity, Model of artery-vein bypass thrombosis, Plasminogen activivator