憂鬱症是全球常見的精神疾病之一，而具有快速抗憂鬱作用的氯胺酮可能藉由促進星狀膠細胞中Gαs蛋白轉位與質膜膽固醇重新分布，進而調控脂筏性質及膜組織。然而，氯胺酮所致的膜結構調控機制與其抗憂鬱作用的分子基礎，目前仍未明確。本研究以特定脂質組成建立仿生脂質膜模型，並製備多層囊泡與大單層囊泡，透過小角度X光散射（SAXS）及螢光光譜分析脂質膜中液態有序相（Lo）與液態無序相（Ld）的相分離行為，以及探討氯胺酮對膜融合的影響。SAXS擬合結果顯示，氯胺酮較偏好分布於Lo相。同時，隨氯胺酮濃度增加，脂質膜由兩相共存轉變為單一相的溫度提高，使 Lo/Ld 兩相共存結構得以維持至較高溫度，顯示氯胺酮可能提高脂筏結構的穩定性，而非促使其瓦解；相較之下，螢光光譜所判定的特徵溫度並未明顯改變，此差異可能與兩種分析技術所反映的膜性質不同有關。此外，利用囊泡內容物混合所產生的螢光訊號評估膜融合程度，結果顯示氯胺酮並未造成明顯改變。本研究結果可提供氯胺酮與脂質膜交互作用及其可能調控脂筏行為的進一步資訊。;Depression is a common psychiatric disorder， and ketamine， which produces rapid antidepressant effects， may regulate lipid raft properties and membrane organization by promoting Gαs translocation and cholesterol redistribution in astrocyte membranes. However， the mechanisms underlying ketamine-induced membrane modulation and its relationship to ketamine′s antidepressant effects remain unclear. In this study， biomimetic membranes with a defined lipid composition were prepared as multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs). Small-angle X-ray scattering (SAXS) and fluorescence spectrometry were used to examine phase separation between liquid-ordered (Lo) and liquid-disordered (Ld) phases and to investigate the effects of ketamine on membrane fusion. SAXS fitting results showed that ketamine preferentially partitioned into the Lo phase， and that with increasing ketamine concentration， the temperature at which the membrane transitioned from two-phase coexistence to a single phase increased， allowing Lo/Ld phase coexistence to persist to higher temperatures. This suggests that ketamine may enhance the stability of raft-like membrane structures rather than promote their disruption. In contrast， the characteristic temperature determined by fluorescence spectrometry remained largely unchanged， and this difference may be attributed to the different membrane properties reflected by the two analytical techniques. In addition， membrane fusion was assessed by fluorescence generated upon vesicle content mixing. The results showed that ketamine did not significantly alter membrane fusion under the lipid composition and experimental conditions used in this study. These findings provide further insight into the interactions between ketamine and lipid membranes and its potential effects on lipid raft behavior.
