Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, Hubei, China.
Sleep Breath. 2020 Dec;24(4):1613-1621. doi: 10.1007/s11325-020-02030-3. Epub 2020 Mar 13.
Obstructive sleep apnea (OSA) in humans chronically promotes the neuronal damage in the hippocampus. Toll-like receptor 2 (TLR2) is pivotal for the development of numerous hippocampal diseases. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA. Here in our study, the effects of TLR2 antagonism on the neural damage elicited by CIH were examined.
Ortho-vanillin (O-vanillin) is an inhibitor of TLR2. Adult male mice were subjected to 8 h of intermittent hypoxia per day with or without O-vanillin for 28 days. Neuronal damage, the number of microglia, the interaction of TLR2 with its adapter protein myeloid differentiation factor 88 (MYD88), the expressions of inflammatory cytokines, and the oxidative stress were observed.
O-vanillin inhibited the increased interaction of TLR2 and MyD88, the activation of NFκB, the aggregation of microglia, the overexpression of proinflammatory agents, the elevation of oxidative stress, and hippocampal neuron cell apoptosis induced by CIH.
Our experiments indicate that TLR2 antagonism may alleviate the hippocampal neuronal damage caused by CIH via inhibiting neuroinflammation and oxidative stress.
在人类中，阻塞性睡眠呼吸暂停（OSA）会慢性促进海马体的神经元损伤。Toll 样受体 2（TLR2）对于许多海马体疾病的发展至关重要。慢性间歇性低氧（CIH）是 OSA 的一个突出特征。在本研究中，我们研究了 TLR2 拮抗作用对 CIH 引起的神经损伤的影响。
香草醛（O-vanillin）是 TLR2 的抑制剂。雄性成年小鼠每天接受 8 小时的间歇性低氧，或在接受间歇性低氧的同时给予 O-vanillin，共 28 天。观察神经元损伤、小胶质细胞数量、TLR2 与其衔接蛋白髓样分化因子 88（MYD88）的相互作用、炎症细胞因子的表达和氧化应激。
O-vanillin 抑制了 CIH 诱导的 TLR2 和 MyD88 相互作用增加、NFκB 激活、小胶质细胞聚集、促炎物质过度表达、氧化应激升高以及海马体神经元细胞凋亡。
我们的实验表明，TLR2 拮抗作用可能通过抑制神经炎症和氧化应激减轻 CIH 引起的海马体神经元损伤。
