Research On The Protection Of Urokinase With And Without Edaravone In Focal Cerebral Ischemia Model In Rats

Objective To explore the neuroprotective mechanism of edaravone after thrombolytic therapy by studying the effect of edaravone on the nitric oxide(NO),matrix metal- oproteinase-9(MMP-9) expression, blood-brain barrier (BBB) following thrombolytic therapy in urokinase after focal cerebral ischemia in rats.Methods The middle cerebral artery (MCA) of Sprague-Dawley rat was occluded by autologous blood clots.Urokinase was administrated by intravenous injection after 2 hours. Rats were randomly assigned to sham-operated group(sham group), saline control group(NS group), urokinase therapy group(UK group) and urokinase with edaravone group(UK+ED group). The infarction volume of brain was investigated by 2,3,5-Triphenyl tetrazolium chloride (TTC) coloring. The histological morphlogical damage of brain was investigated by hematoxylin -eosin (HE) staining. Nitrite reduction method was used to detect the content of NO. The expression of matrix MMP-9 in brain tissue was observed by immuno- histochemistry. The permeability of blood-brain barrier (BBB) was evaluated based on leakage of Evans blue and the content of EB in the brain tissue was measured by spectrophotometry.Results 1. Contrast to NS group, urokinase significantly reduced the cerebral infarct volume percentage (P<0.01); In UK+ED group, the cerebral infarct volume percentage is further reduced (P<0.05).2. In UK group,there are six rats been found that urokinase significantly ameliorated the histopathological damage in brain,one rats been found erythrocyte leak out capillary in brain, one rats been found hemorrhagic focus in brain. In UK+ED group, the histopathological damage in brain is futurer ameliorated,all rats been not found erythrocyte leak out capillary and hemorrhagic focus in brain.3. Contrast to UK group,the combination of UK and ED significantly reduced NO content in the side of ischemia brain(P<0.01). 4. Contrast to UK group, the combination of UK and ED significantly decreased MMP-9 expression in the side of ischemia brain(P<0.01).5. Contrast to UK group, the combination of UK and ED significantly reduced EB content in the side of ischemia brain(P<0.01).Conclusion 1.Urokinase thrombolytic therapy significantly reduced the infarct size. urokinase with edaravone group 2. The breakdown of blood-brain barrier occurred after urokinase thrombolytic therapy .NO and MMP-9 involved in the pathological process. 3. It is assumed that edaravone may inhibit MMP-9 expression by reduce the production of NO, then relieve the damage of reperfusion to BBB,and may prolong the thrombolytic therapeutic time window.