硫化氢减轻脑缺血后tPA导致脑出血-神经生物学专业论文.docxVIP

II II 中文摘要 硫化氢减轻脑缺血后 tPA 导致的脑出血 转角测试和转棒实验的行为学测试，结果显示， ADT-OH 减轻了 MCAO 及 tPA 处理 导致的小鼠神经功能损伤。ADT-OH 对 MCAO 及 tPA 处理后 1 天的梗死体积影响不 大，但是减轻了 MCAO 及 tPA 处理后第 7 天 tPA 导致的梗死体积增加。明胶酶谱显 示，脑缺血导致 MMP-9 活性上升；tPA 提高了缺血侧脑中 MMP-9 活性；ADT-OH 降 低了缺血侧 tPA 引起的 MMP-9 活性的上升。 创新：首次发现 H2S 供体，能够减轻脑缺血后 tPA 导致的脑出血。 结论：H2S 供体能明显减轻脑缺血后 tPA 导致的脑出血，促进神经功能恢复。H2S 供体可能成为今后脑卒中后 tPA 导致的脑出血的新的药物治疗手段。 关键词：硫化氢；组织纤溶酶原激活酶（tPA）； H2S 供体；基质金属蛋白酶 （MMP-9） 作 者：刘 辉 指导教师：程 坚 教授 PAGE PAGE IV Hydrogen Sulfide Reduces tPA-Induced Cerebral Hemorrhage after Ischemic Stroke Abstract Hydrogen Sulfide Reduces tPA-Induced Cerebral Hemorrhage after Ischemic Stroke Abstract Objective: The thrombolytic agent tissue plasminogen activator (tPA) remains the only drug approved by Food and Drug Administration (FDA) for the treatment of ischemic stroke. However, very few patients could benefit from it since it has narrow time window and increases the risk of cerebral hemorrhage. Hydrogen sulfide (H2S) has been recognized as the third gaseous signal molecule in addition to nitric oxide (NO) and carbon monoxide (CO). We investigated whether H2S alleviated cerebral hemorrhage transformation associated with tPA therapy following stroke. Methods: C57/BL6J male mice were subjected to middle cerebral artery occlusion (MCAO). Glucose (6 ml/kg, 50%w/v) was intraperitoneally injected 15 min before MCAO. tPA (10 mg/kg) or saline (4 ml/kg) was administered from femoral vein immediately after reperfusion, followed by intraperitoneal injection of H2S donors or vehicle. The mice were divided into six groups: Sham ， control group, tPA group, tPA+NaHS group, tPA+ADT group, tPA +ADT-OH group. Cerebral hemorrhage was examined by assessing hemoglobin content in the brain with a commercial kit at 24 hours after reperfusion. Infarct volumes were assessed by 2, 3, 5-triphenyltetrazolium chloride (TTC) histology at 1 day and 7 days after MCAO. Blood-brain barrier permeability was evaluate