Effects of urokinase thrombolysis on matrix metalloproteinase-9, blood-brain barrier permeability and intracerebral hemorrhage in a rat model of middle cerebral artery thromboembolism

Abstract

Objective To observe the effects of the expressions of matrix metalloproteinase-9 （MMP-9）, intracerebral hemorrhage volume and blood-brain barrier permeability after embolic cerebral ischemia and thrombolysis with urokinase （UK） and to investigate the relationship between MMP-9 and blood-brain barrier permeability and intracerebral hemorrhage after thrombolysis. Methods A rat model of middle cerebral artery occlusion was established by intracarotid injection of autologous blood clots. UK was given intravenously at 6 hours after ischemia. After 24 hours, the expressions of MMP-9 in brain tissue, blood-brain barrier permeability, cerebral infarct volume, and intracerebral hemorrhage volume were detected by the immunohistochemical method, Evans blue extravasation method, TTC staining method, and spectrophotometric method, respectively. Results The expressions of MMP-9 in a cerebral ischemic group were significantly higher than those in a sham-operation group （P 〈 0.01 ）, and in the UK group they were significantly higher than those in the cerebral ischemic group （P 〈 0. 01）. The Evens blue content in the cerebral ischemic group was 5774.00 ＋ 1659. 70 ng/g, which was significantly higher than 643.33 ± 151.34 ng/g in the sham-operation group （P 〈 0.01 ）, and in the UK group was 6283.83 ± 1099. 28 ng/g, there was a tendency higher than in the cerebral ischemic group. 1he intracerebral hemorrhage volumes in the UK and cerebral ischemic groups were 3.16 ±8.84 μl （median ± quartile） and 0. 00 ± 1.48 μl, respectively, and the incidences of intracerebral hemorrhage were 25.00% % and 4. 17%, respectively. Conclusions UK thrombolysis may upregulate the expressions of MMP-9, and its expressions are associated with the increased blood-brain barrier permeability and intracerebral hemorrhage after thrombolysis. Key words: urokinase; intracranial embolism and thrombosis; matrix metalloproteinase 9; thrombolytic therapy; blood-brain barrier; rats