氧化应激反应在脑出血继发性损伤病理机制中起着重要作用。研究表明，Astaxanthin（AST）具有强大的抗氧化能力。我们前期研究发现，AST可以减轻脑出血继发性损伤，并发现AST治疗后，血肿周围脑组织Nrf2蛋白水平明显升高。Nrf2/ARE通路是机体抵抗氧化应激损伤的最主要内源性通路。研究表明，PI3K/Akt对诱导激活Nrf2/ARE通路有重要作用。据此，我们推测“AST通过激活PI3K/Akt-Nrf2/ARE通路，提升机体抗氧化能力，减轻脑出血后氧化应激损伤，发挥神经保护作用”。本项目拟在前期研究基础上，进一步明确AST的脑保护作用，摸索其治疗脑出血的量效关系及治疗时间窗。并通过体内、体外模型，结合基因敲除小鼠，RNA干扰技术，借助免疫组化，Western blot，RT-PCR，EMSA，双荧光素酶报告基因检测等多种技术反复验证此假说。本项目将为脑出血的治疗提供新的思路和策略。

Oxidative stress is one of the important pathological pathways associated with secondary brain injury after ICH. Astaxanthin (AST) is reported to have powerful antioxidant activity. Our previous research found that AST could ameliorate the secondary brain injury after ICH. Besides, we found that AST administration after intracerebral hemorrhage (ICH) significantly enhanced Nrf2 protein in the perihematoma tissue. Nrf2/ARE is recognized as major endogenous regulatory system against oxidative injury. It was reported that PI3K/Akt was essential for the activation of Nrf2/ARE pathway. Therefore, we hypothesized that AST could ameliorate the secondary brain injury after ICH through inducing the activation of Nrf2/ARE, which is mediated by the PI3K-Akt pathway. In this study, we would estimate the neuroprotective effect against ICH of AST in different concentration and survey the therapeutic time window to further confirm the neuroprotective role of AST on ICH. Besides, we would test our hypothesis in vivo and in vitro by using various techniques including immunohistochemistry, Western blot, RT-PCR, EMSA, Dual Luciferase Reporter Gene Assay with genetically knockout mice and RNA interference. This study could provide valuable information for the ICH therapy.