Rosiglitazone attenuates hyperglycemia-enhanced hemorrhagic transformation after transient focal ischemia in rats

Rosiglitazone attenuates hyperglycemia-enhanced hemorrhagic transformation after transient focal ischemia in rats
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罗格列酮减轻大鼠短暂局灶性缺血后高血糖增强的出血转化

DOI:
10.1016/j.neuroscience.2013.07.039
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发表时间:
2013-10
期刊:
影响因子:
3.3
通讯作者:
Lou, M.
Lou, M.
中科院分区:
医学3区
文献类型:
--
作者:
Huang, H. G.;Sun, J. Z.;Wen, S. Q.;Lou, M.

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出血性转化(HT)被认为是静脉注射组织型纤溶酶原激活剂(t-PA)治疗最可怕的并发症。在本研究中,我们在大鼠局灶性脑缺血模型上检测了罗格列酮对羟色胺的影响。雄性SD大鼠腹腔注射50%葡萄糖(6ml/kg),10min后造成大脑中动脉阻塞(MCAO),用激光多普勒血流仪活体监测局部脑血流量。两组均为罗格列酮治疗组和赋形剂组。治疗组缺血1.5h后,再灌流开始时给予罗格列酮(2 mg/kg)。于缺血后24 h检测神经行为评分、脑梗塞体积、血红蛋白渗漏、出血率、IV型胶原和葡萄糖转运蛋白1(GLUT1)的表达。与赋形剂组相比,罗格列酮可改善神经行为缺陷,减少脑梗塞体积和出血率,并抑制血红蛋白渗漏。此外,与赋形剂组相比,它还增加了IV型胶原和GLUT1的表达。我们的结果提示,罗格列酮减轻MCAO后高血糖诱导的高血压,可能是通过保留GLUT1的表达。
Hemorrhagic transformation (HT) has been claimed to represent the most feared complication of treatment with intravenous tissue plasminogen activator (t-PA) therapy. In this study, we tested the effect of rosiglitazone on HT in a rat focal cerebral ischemia model. Male Sprague–Dawley rats received an injection of 50% dextrose (6 ml/kg intraperitoneally) and were subjected to middle cerebral artery occlusion (MCAO) 10 min later, with the regional cerebral blood flow monitoredin vivoby laser-Doppler-flowmetry. Two groups were included: rosiglitazone treatment and vehicle group. In the treatment group, after 1.5 h of ischemia, rosiglitazone (2 mg/kg) was administered at the onset of reperfusion. Neurobehavioral scores, infarct volume, hemoglobin leakage, hemorrhage rate, the expression of collagen IV and glucose transporter 1 (GLUT1) were measured at 24 h after ischemia. Rosiglitazone improved neurobehavioral deficits, reduced infarct volume and hemorrhage rate, and inhibited hemoglobin leakage, when compared with the vehicle group. In addition, it increased the expression of collagen IV and GLUT1 compared to the vehicle group. Our results suggest that rosiglitazone attenuated the hyperglycemia-induced HT after MCAO, possibly by preservation of GLUT1 expression.
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