阻塞性睡眠呼吸暂停低通气综合征可导致神经认知功能障碍。这与其间歇低氧（IH）致小胶质细胞炎症有关，但未知是否影响小胶质细胞极化。我们前期研究示IH诱导小胶质细胞中SENP1表达水平下调，SENP1过表达可显著抑制由IH引起的炎症反应并降低细胞凋亡率，而SENP1是Sharp-1去SUMO化修饰的关键酶，可通过影响Sharp-1的SUMO化修饰，调控PPARγ表达水平。鉴于PPARγ在小胶质细胞极化中有重要作用，并基于我们前期结果，我们推测IH诱导小胶质细胞SENP1下调，引起Sharp-1的SUMO化修饰增加，PPARγ表达下降，导致M1型极化比例上升，M2型极化比例下降，神经炎症反应加剧，诱导神经损伤。本研究拟通过体外实验研究IH对小胶质细胞极化的影响，明确SENP1在小胶质细胞极化中的作用及机制，并通过体内动物模型加以验证。本研究为进一步防治该疾病的神经系统并发症提供理论基础和新靶点。

Obstructive sleep apnea hypopnea syndrome (OSAS) can induce neurocognitive dysfunction, which is contributed to the inflammatory reaction of microglia caused by intermittent hypoxia (IH). However, the specific mechanism has not yet been elucidated. In our previous work, we found that expression of SENP1 was down-regulated by IH in BV2 cells, and over-expression of SENP1 could significantly inhibit the up-regulation of expression of proinflammatory factors induced by IH, thus inhibiting microglial inflammation and reducing the rate of cell apoptosis. Other studies have shown that SENP1 is a protease that specifically de-SUMOylates SUMOylated Sharp-1, while Sharp-1 is a transcriptional inhibitory factor regulating PPARγ activity. Based on the key role of PPARγ in regulating microglia polarization and our previous results, we speculate that SENP1 promotes M1 polarization as well as inhibits M2 polarization through increasing SUMOylation of Sharp-1 thus inhibiting PPARγ expression, finally aggravates neuroinflammation and causes neurotrosis. In this research, we intend to explore role of SENP1 on microglia M1/M2 polarization in IH condition and the mechanism, clarifying its role in neuroinflammation and verifying the results by animal model. This study could benefit further understanding of neurocogtive dysfunction caused by OSAS and provide theoretic basis and potential new target for prevention and treatment.