Objective: This study was designed to use urokinase (UK) in combination with batroxobin in thrombolytic therapy so as to see whether batroxobin(DF-521) would be effective for neuroprotection.

Methods: The model of right middle cerebral artery occlusion (MCAO) in male SD rats was established. 120 rats were randomized into 9 groups, namely control group, sham control group, and groups that were treated with batroxobin and urokinase together or separately. Each group comprised 15 rats. Intracranial bleeding, infarct volume ratio and neurological function were observed.

Results: Intracranial bleeding was found in 5 rats of the UK 5000 U/kg group, in 4 rats of the UK 5000 U/kg (2 h) + DF-521 5 BU/kg (2 h) group, and in only 1 rat of the UK 5000 U/kg (2 h) + DF-521 5 BU/kg (1 h) group. Cerebral infarct volume ratio was obviously reduced in 5 BU/kg batroxobin group. No difference was observed in neurological deficit scores.

Conclusion: 5000 U/kg urokinase increased the risk of intracranial hemorrhage in rat MCAO model. Batroxobin either used separately or in combination with urokinase would not increase the risk of intracranial hemorrhage in rat MCAO model.

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