铁超载引起神经元迟发性损伤是脑出血（ICH）病人预后差的关键因素，尚无有效干预方法。低浓度铁是脑出血后迟发性损伤的关键切入点，我们前期报道了低浓度铁离子可引起神经元线粒体CypD乙酰化介导的线粒体功能障碍，但其在神经元迟发性损伤中的作用及机制不清。最新研究报道在293T细胞中，线粒体应激引起DELE1转位至细胞质，激活转录因子ATF4引起转录异常及细胞功能障碍。预实验结果显示线粒体CypD乙酰化抑制剂可改善低浓度铁超载引起的神经元转录异常与突触损伤。据此推测：ICH慢性期血肿周围低浓度铁超载引起神经元线粒体CypD乙酰化，进一步诱导DELE1转位/ATF4激活导致神经元损伤。此外，血肿周轴突线粒体CypD乙酰化/DELE1转位或介导ICH后逆行性皮层神经元损伤。本课题拟探讨ICH后CypD乙酰化促进DELE1转位在神经元迟发性损伤的作用及机制，旨在为ICH后神经元迟发性损伤提供干预策略。

Delayed neuronal injury is an important factor of poor prognosis in patients after intracerebral hemorrhage (ICH), and there is no effective intervention. Low concentration of iron overload around the hematoma is a key factor contributing to delayed neuronal injury after ICH. Our previous studies have confirmed that low concentration of iron can induce neuronal mitochondrial CypD acetylation and mitochondrial dysfunction in neuron, however, its role and mechanism in delayed neuronal injury are unclear. In 293T cells, mitochondrial stress induced translocation of DELE1 from mitochondria to cytoplasm, which may lead to ATF4 pathway-related transcriptional abnormalities and cell dysfunctions. Our preliminary study found that inhibitors of mitochondrial CypD acetylation can alleviate the neuronal transcription abnormality and synaptic damage induced by low concentration of iron overload. It is speculated that low concentration of iron overload induced neuronal CypD acetylation may result in mitochondrial stress and the subsequent DELE1 translocation, leading to abnormal ATF4 pathway activation and finally the delayed neuronal injury. Similar mechanisms may also exist in retrograde cortical neuronal injury caused by axonal mitochondrial CypD acetylation of the basal ganglia. The purpose of this study is to explore the mechanism of mitochondrial CypD acetylation induced DELE1 translocation in delayed neuronal injury after intracerebral hemorrhage and so as to provide intervention targets and strategies for delayed neuronal injury after ICH.