血脑屏障通透性在犬脑梗死溶栓后颅内出血转化发病机制和早期预测作用中的研究

Hemorrhagic transformation (HT), following by thrombolytic therapy of acute cerebral ischemia, is one of the independent risk factors for poor prognosis. It reported that acute ischemic stroke and transarterial injection tissue plasminogen activator (t-PA) which disrupted the blood-brain barrier (BBB) permeability, and eventually contributed and exacerbated to HT. Previous studies were mostly based on establish ischemia stroke models or transient ischemia-reperfusion models by embolizing with thread in rats and other small animals. And those results were difficult to conduct clinical transformation. Furthermore, it is still unclear that the relevant between BBB permeability and the pathogenesis of HT after thrombolytic therapy, even whether BBB permeability could early prediction of HT. Therefore, based on our canine ischemia stroke model, we intend to explore: (1) establish a HT model after thrombolytic therapy of acute cerebral ischemia through interventional methods; (2) assessment the cerebral infarction and the BBB permeability, the dynamic time-quantity changes of BBB permeability, the effect of BBB permeability on the HT and its early detection for HT by using multi-modal MRI and especially dynamic contrast enhanced-MRI. These results will help for prediction and improvement the prognosis of cerebral infarction, and provide the basis for searching effective prevention and treatment strategies in clinic patients.

急性脑梗死溶栓治疗后的颅内出血转化，是影响患者预后的独立危险因素。急性脑梗死及后续注射组织纤维蛋白酶原激活剂行动脉溶栓治疗，均可破坏血脑屏障通透性，导致颅内出血转化比例和严重程度增加。前期以鼠等小动物建立线栓栓塞性脑梗死或短暂性脑缺血再灌注模型，相关结果不能有效进行临床模拟转化。并且，血脑屏障通透性的动态变化与脑梗死溶栓后出血转化机制以及能否早期预测出血转化的发生亦尚不明确。因此，我们拟在前期基础上，探讨：①通过介入方法建立血栓栓塞性脑梗死溶栓后颅内出血转化模型；②采用多模态MR，尤其MR动态增强成像评估脑梗死及血脑屏障通透性的动态变化，绘制脑梗死后血脑屏障通透性变化的时间-量效曲线，研究血脑屏障通透性改变对出血转化的影响及早期预测作用，为判断和改善脑梗死预后提供新的研究依据，从而为其临床寻找有效的预防和治疗方案。

急性脑梗死溶栓治疗后的颅内出血转化，是影响患者预后的独立危险因素。急性脑梗死及后续注射组织纤维蛋白酶原激活剂行动脉溶栓治疗，均可破坏血脑屏障通透性，导致颅内出血转化比例和严重程度增加。前期以鼠等小动物建立线栓栓塞性脑梗死或短暂性脑缺血再灌注模型，相关结果不能有效进行临床模拟转化。并且，血脑屏障通透性的动态变化与脑梗死溶栓后出血转化机制以及能否早期预测出血转化的发生亦尚不明确。本项研究通过MRI和血栓弹力图对不同成分血栓的血栓强度等特性以及MRI成像特点进行了体外研究，揭示了血栓中不同含量红细胞与磁共振信号值的相关性，主要表现为随红细胞比例增加，T1WI及T2WI值减低。在体内实验中，我们通过静脉给与RTPA成功建立了犬脑梗死后出血转化模型，并对其潜在机制进行了探讨。我们的结果表明，RTPA引起的颅内出血转化的潜在机制可能与MMP-9表达增加，继而引起的血脑屏障功能障碍有关。上述研究结果将为进一步明确急性脑梗死溶栓治疗后的颅内出血转化机制提供了新的实验理论证据。