脑缺血再灌注中高尔基体碎裂是造成神经功能缺损的重要原因，是神经保护治疗的重要靶点。高尔基体的稳定与tubulin乙酰化密切相关，HDAC6是催化tubulin去乙酰化的关键酶。我们前期研究发现，神经细胞氧糖剥夺再灌注后，HDAC6活性增加，tubulin乙酰化减少，高尔基体发生明显的碎裂，而抑制HDAC6的活性能减轻氧糖剥夺再灌注后高尔基体的碎裂，发挥神经保护作用。因此，本研究中，我们在前期研究的基础上，通过体内、外实验，检测脑缺血再灌注中HDAC6活性改变及机制；系统验证HDAC6抑制在脑缺血再灌注中对高尔基体及神经细胞的保护作用；进一步证实HDAC6抑制通过调节tubulin乙酰化而减少高尔基体的碎裂；并深入阐明tubulin与FHDC1相互作用改变是tubulin乙酰化减少导致高尔基体碎裂的机制之一。本项目的实施将有助于扩展对脑缺血再灌注发生机制的认识，并为治疗提供潜在的靶点和手段。

Golgi fragmentation is an important cause of neurological deficit in cerebral ischemia-reperfusion injury. Protection of the structure and function of Golgi apparatus is of great significance against cerebral ischemia-reperfusion injury. The stability of Golgi is closely related to tubulin acetylation. HDAC6 is a key enzyme that catalyzes the deacetylation of tubulin. Our preliminary data show that oxygen-glucose deprivation/reperfusion (OGDR) increases HDAC6 activity, reduces tubulin acetylation and induces Golgi fragmentation in cultured neurons. HDAC6 inhibition protects against OGDR induced Golgi fragmentation. Therefore, based on preliminary findings, in this proposal, we will investigate HDAC6 activity in cerebral ischemia-reperfusion injury and its mechanisms both in vitro and in vivo experiment. We will also determine the neuroprotective effects of HDAC6 inhibition on Golgi apparatus and neurons in cerebral ischemia-reperfusion injury. We will further confirm that HDAC6 inhibition reduces Golgi fragmentation by regulating tubulin acetylation. Finally, we will clarify the alteration of interaction between tubulin and FHDC1 is one of the mechanisms that reduced tubulin acetylation induces Golgi fragmentation. The successful implementation of this project will contribute to expand understanding of the pathogenesis of cerebral ischemia reperfusion injury, while providing potential targets for intervention and treatment.