국소 허혈성 뇌졸중 후 조직 플라즈미노겐 활성제를 투여한 당뇨쥐에서의 미세혈관반응

Abstract

Background: Diabetes mellitus (DM) or hyperglycemia is known to be associated with increased risk of intracranial hemor-rhage in acute stroke patients who are treated with IV tissue-type plasminogen activator (tPA). However, the underlying mechanism remains unknown. We tested the hypothesis that different expression of matrix metalloproteinase (MMP) and occludin in DM play a role in increased risk of hemorrhages in DM by using a diabetic rat model.

Methods: DM was induc-ed in Spargue Dawley rats by using injection of streptozotocin (60 mg/kg) and harvesting for 20 weeks. Focal cerebral ischemia was induced by occlusion of the middle cerebral artery occlusion (MCAO) for 2 hours and then reperfusion for 18 hours by using a nylon thread. tPA (10 mg/kg) or normal saline was infused via the femoral vein. Spectrophotometry, western blot and zymography were performed to measure the amount of hemorrhages, levels of occludin (tight junction protein) and activity of matrix metalloproteinase (MMP)-2 and MMP-9, respectively.

Results: Mortality was significantly higher in diabetic rats. In surviving rats, hemorrhagic amounts and levels of cerebral occludin were not different between diabetic and nondiabetic rats, and tPA-infused and normal saline-infused rats. Although MMP-9 were higher in ischemic groups (P=0.001), their activities were not changed in diabetic or tPA-treated rats.

Conclusion: Occludin and MMP may not play a major role in increasing the risk of hemorrhage in diabetic rats.