深部脑刺激下丘脑视内侧核引发亚低温的机制及对脑缺血损伤保护作用的研究

脑卒中是一种高致残率和高死亡率的血管性疾病，然而治疗方法十分有限。亚低温对脑卒中具有显著的神经保护作用，但物理体表降温作为现有的低温诱导手段，不仅降温效率低，而且会产生极度不适感，并引起严重的不良反应，如寒战、脏器损伤等，这些都极大地影响了亚低温治疗的 效果并限制了临床上的应用，亟需发现更好的亚低温诱导方法。

恒温动物的体温调节中枢位于下丘脑视前区。研究显示，激活下丘脑视前区 (Preoptic Area, POA) 中负责感受热温度的神经元可以显著降低体温。因此，本研究首先采用化学遗传学的方法，激活视前区中 Vglut2+神经元，这种方式不仅使小鼠核心体温降低到 30℃，而且显著降低了局灶性脑缺血再灌注损伤，并且不会引起寒战等冷应激副反应。在此基础上，本研究首次利用深部脑刺激 (Deep Brain Stimulation, DBS) 技术双侧刺激下丘脑内侧视前核 (Median Preoptic Nucleus, MPN) 区域。通过对刺激电压、频率、持续时间的优化，发现使用 4V, 100Hz, 90us 的参数，能使小鼠核心体温在电刺激 30 分钟后下降至 32-34℃，呈现亚低温状态，而不会引起寒战、血糖升高及去甲肾上腺素升高等冷应激反应。在代谢方面，小鼠表现为氧气消耗量、产热及呼吸交换率降低的低代谢特征。因此，DBS 能够介导小鼠低温低代谢的类蛰眠状态。深部脑刺激 MPN 形成的类蛰眠状态可显著降低小鼠局灶性脑缺血再灌注损伤，表明这种方法潜在的临床应用价值。进一步研究发现，其主要通过激活温敏神经元，实现了亚低温状态的介导。

综上所述，本研究使用深部脑刺激技术，通过双侧刺激下丘脑 MPN 中的温敏神经元诱发了小鼠的亚低温状态。其作为一种治疗手段显著降低了脑缺血再灌注损伤。与传统的物理降温相比，该方法有效避免了寒战等冷应激反应，也消除了潜在的脏器损伤等副作用，为脑卒中的低温治疗提供了新手段。 

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