脂筏（lipid raft）理論的觀點：Omega -3多元不飽合脂肪酸與憂鬱症及心血管疾病之關係

The Lipid Raft Hypothesis: The Relation among Omega-3 Fatty Acids, Depression and Cardiovascular Diseases

前言：世界衛生組織指出，憂鬱症及心血管疾病即將於西元2020年成為兩大最主要提早死亡及失能的原因。憂鬱症經常合併心血管疾病，而身體症狀更是憂鬱症患者就醫之主因，再加上傳統單胺酸作用的抗憂鬱劑療效並不理想，種種現象皆顯示出目前最盛行的單胺酸假說在探討憂鬱症的病因上之不足。方法：我們回顧了所有omega-3多元不飽合脂肪酸（縮寫為n-3PUFAs，或俗稱深海魚油）與脂筏(lipidrafts)相關的近期發表文獻並進一步探討他們在心血管疾病與憂鬱症所扮演的角色。結果：在文獻回顧中，從流行病學、神經生理學及療效研究中發現，n-3PUFAs分別與心血管疾病和憂鬱症的病因都有密切的關連，omega-3PUFAs是人類生存的必需脂肪酸，具有神經功能維護及抑制過度發炎反應的生理功能，也可以影響「下視丘－－腦垂體－－腎上腺軸」所引發的自律神經系統的功能。因此探討憂鬱症的病因，除了最盛行的血清素（單胺酸）假說外，脂肪酸假說是目前一個前瞻且重要的方向。近期的研究發現脂筏，是一種細胞膜上富含cholesterol及sphingolipids之特殊脂類、且對界面活性劑有抗性的特殊微小構造。脂筏可藉由提供功能性的膜環境來調控細胞中重要的生理反應，例如：訊息傳遞、細胞膜上分子運輸、可塑性、移動、防衛及免疫系統。由於基礎研究與動物研究發現，omega-3PUFAs具有調控脂筏的功能，亦可影響細胞間訊息傳遞及分子運輸，更能進一步調節內分泌、自律神經及免疫系統等功能。結論：因此，本文將探討omega-3多元不飽合脂肪酸的調控脂筏功能及其在於心血管疾病與憂鬱症中所扮演的角色。希望能藉由更多脂筏與omega-3多元不飽合脂肪酸的研究，可以提供給「傷心」的病人更好的治療。

Background: Depression and cardiovascular diseases (CVDs) exist frequently as comorbid conditions, suggesting their common etiologies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play important roles in infl ammation and brain functions, and they appear to be a possible interface between depression and CVDs. Methods: We reviewed all recently published papers on n-3 PUFAs and lipid rafts to look for their implications in causing CVDs and depression. Results: In the literature, we found that lipid raft formations and disruptions are critically important in regulating of neurotransmission signaling and receptor functions, which in turn might be involved in causing depression and CVDs. In addition to neurotransmission, n-3 PUFAs have shown to possibly regulate immunity and neuroendocrine function via lipid raft modulations. Conclusion: This review has provided evidences for the role of n-3 PUFAs in causing depression and CVD. We also propose a new hypothesis about cellular mechanisms mediated by lipid rafts.