IGF-1调控STAT3参与OSAS大鼠认知功能障碍的机制研究

Obstructive sleep apnea syndrome（OSAS） is closely related to the Cognitive dysfunction, but its specific molecular signaling mechanism is not clear. Synaptic plasticity can affect cognitive function, and Signal transducer and activator of transcription-3(STAT3) can regulate synaptic plasticity. Some physiology and pathophysiology functions of insulin-like growth factor-1 (IGF-1) have been confirmed by regulating STAT3 signaling pathway.In addition, there have been reported that OSAS patients with nocturnal hypoxemia resulting decreased serum IGF-1 level may be associated with cognitive impairment. Our preliminary work revealed that apoptosis of hippocampal neurons could be induced by OSAS in rats. Whether IGF-1 regulates STAT3 signaling pathway is involved in cognitive dysfunction after OSAS has not been reported in the literature. The project intends to use the recombinant IGF-1 and STAT3 specific inhibitor to observe animal behavior, electroencephalogram and electrophysiology changes, and detect the expression of hippocampus related proteins by molecules biology techniques. At last, it will reveal the formation mechanism of cognitive dysfunction after OSAS from the perspective of molecular signaling pathway, and provide a new target for its prevention.

阻塞性睡眠呼吸暂停综合征（OSAS）与认知功能障碍密切相关，但其发生的具体分子信号机制尚不清楚。突触可塑性的变化可以影响认知功能的改变，而信号转导及转录活化蛋白-3（STAT3）可以调控突触可塑性；胰岛素样生长因子-1（IGF-1）已经被证实可以通过调控STAT3信号通路而行使一定的生理和病理生理功能，此外，又有报道称，OSAS患者的夜间低氧血症所导致血清中IGF-1水平下降可能与认知功能损害有关。研究者的前期工作已经发现OSAS可导致大鼠海马神经元凋亡。IGF-1调控STAT3信号通路是否参与OSAS后认知功能障碍尚未见文献报道。本项目拟通过重组IGF-1和STAT3特异性抑制剂的干预，观察动物脑电行为学和膜片钳系统监测电生理变化，分子生物学技术检测海马各区相关分子的表达情况，从而，从分子信号通路机制的角度揭示OSAS认知功能障碍的形成机制，期望为其防治提供新的

阻塞性睡眠呼吸暂停综合征（OSAS）与认知功能障碍密切相关，但其发生的具体分子信号机制尚不清楚。突触可塑性的变化可以影响认知功能的改变，而信号转导及转录活化蛋白-3（STAT3）可以调控突触可塑性；胰岛素样生长因子-1（IGF-1）已经被证实可以通过调控STAT3信号通路而行使一定的生理和病理生理功能。通过慢性间歇性缺氧模拟OSAS发病过程建立OSAS模型大鼠出现学习记忆等认知功能损害，OSAS大鼠中P-STAT3表达增加、PSD95、p-IGF-1R及SYP表达下降，IGF-1 可改善 OSAS 大鼠的学习记忆能力，这可能与海马 p-IGF-1R、SYP蛋白表达水平升高，抑制STAT3信号通路后可降低P-STAT3表达，PSD95表达增加，改善OSAS大鼠认知障碍。在研究期间共发表论文19篇，其中包括1篇SCI期刊，18篇核心期刊。本研究主要以OSAS大鼠为主要研究对象，为某些相关的OSAS后认知障碍治疗提供新的理论依据，为OSAS后认知障碍的深入研究奠定基础。