自发性脑出血（ICH）是中风发病率和死亡率最高的亚型。在脑出血过程中大量的血液释放到细胞间隙，所以血红素的代谢对于机体恢复起非常重要的作用。血红素加氧酶（HO）是一种把死亡细胞中释放的血红蛋白或其他血红素蛋白质降解为游离血红素这一过程的限速酶。中枢神经系统包含两个有活性的HO同工酶：HO-1的和HO-2。我们将首次对这两个同工酶在脑出血中的作用和远期影响进行研究。通过前期的初步研究，我们推测，脑出血后，是HO-1，而不是HO-2，对血脑屏障起破坏作用并加剧脑出血损伤。我们将使用两种脑出血模型模拟临床脑出血，利用HO-1 -/- 和HO-2 -/- 小鼠以及选择性的HO-1的抑制剂OB-24，研究在脑出血损伤中HO-1和HO-2的作用，以确定血红素加氧酶在脑出血中的作用。我们的研究结果将帮助临床确定治疗脑出血的新的药物靶点。

Spontaneous intracerebral hemorrhage (ICH) is the stroke subtype with the highest mortality and morbidity. Because large amounts of blood are released into the extracellular spaces during ICH,the transport and metabolism of free heme is very important for recovery. Heme oxygenase (HO) is the rate-limiting enzyme that degrades free heme derived from hemoglobin and other hemoproteins released from dying cells. The central nervous system contains two active isoenzymes of HO: HO-1 and HO-2. Our long-term objective is to limit ICH-induced brain injury. In working toward that goal, we first propose to identify the role that both HO isoenzyme plays in blood-brain barrier (BBB) disruption and long-term ICH outcomes. Our preliminary data led us to hypothesize that HO-1, but not HO-2, plays a role in BBB disruption and negatively affects ICH outcomes. We will use two established ICH models to mimic clinical ICH and utilize our available HO-1-/- and HO-2-/- mice and selective HO-1 inhibitors. We will determine the role of HO-1 and HO-2 in ICH injury. Our findings could help identify new pharmacological targets for the treatment of ICH that could be tested in future clinical trials.