Early insulin glycemic control combined with tPA thrombolysis reduces acute brain tissue damages in a focal embolic stroke model of diabetic rats.
Early insulin glycemic control combined with tPA thrombolysis reduces acute brain tissue damages in a focal embolic stroke model of diabetic rats.
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DOI：
10.1161/strokeaha.112.663476
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发表时间：
2013-01
期刊：
影响因子：
8.3
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Fan X;Ning M;Lo EH;Wang X
早期胰岛素血糖控制联合组织型纤溶酶原激活剂（tPA）溶栓治疗对中风后高血糖的治疗效果尚未研究，但具有很大的临床意义。在这项研究中，我们测试了胰岛素加 tPA 组合在 I 型糖尿病大鼠局灶性栓塞性中风模型中的作用。使用 STZ 使雄性 Wistar 大鼠产生 I 型糖尿病 6 周，然后诱发栓塞性局灶性中风。所有大鼠在中风后 1 小时接受胰岛素或盐水治疗，然后在 1.5 小时接受 tPA 或盐水治疗。中风后24小时检查死亡率、梗塞、半球肿胀、出血转化和灌注缺陷。通过 ELISA 测定，在中风前、中风后 1.5、3 和 6 小时测量总血浆纤溶酶原激活物抑制剂 - 1 (PAI-1) 抗原和活性水平。单独早期胰岛素血糖控制或单独tPA溶栓对缺血性梗塞没有显着影响。然而，早期胰岛素血糖控制联合 tPA 显着减少了脑梗塞和肿胀，改善了 tPA 相关的出血转化，并改善了中风后 24 小时的血浆灌注。我们还发现，该组合显着降低了中风后 6 小时的血浆 PAI-1 抗原水平以及 1.5 小时和 6 小时的 PAI-1 活性。早期胰岛素血糖控制与 tPA 溶栓联合治疗缺血性卒中合并糖尿病或卒中后高血糖可能有益。
Therapeutic effects of early insulin glycemic control for post-stroke hyperglycemia in combination with tissue-type plasminogen activator (tPA) thrombolytic therapy has not yet been studied but is of great clinical interest. In this study we tested the effects of insulin plus tPA combination in a model of focal embolic stroke in type I diabetic rats. STZ was used to produce Type I diabetes in male Wistar rats for 6 weeks then embolic focal strokes were induced. All rats were treated with insulin or saline at 1 h followed by tPA or saline at 1.5 h after stroke. Mortality, infarction, hemispheric swelling, hemorrhagic transformation and perfusion defects were examined at 24 hours after stroke. Total plasma plasminogen activator inhibitor-1 (PAI-1) antigen and activity levels were measured at before stroke, 1.5, 3 and 6 hours after stroke by ELISA assays. Early insulin glycemic control alone or tPA thrombolysis alone had no significant effects on ischemic infarction. However, early insulin glycemic control combined with tPA significantly reduced brain infarction and swelling , ameliorated tPA-associated hemorrhagic transformation, and improved plasma perfusion at 24 hours after stroke. We also found the combination significantly decreased plasma PAI-1 antigen level at 6 hours, and PAI-1 activity at 1.5 hours and 6 hours after stroke. Early insulin glycemic control may be beneficial in combination with tPA thrombolysis for ischemic stroke with diabetes mellitus or post-stroke hyperglycemia.