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缩醛磷脂

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你大脑里正在消失的防弹衣

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上一期讲极小曲面的时候

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我在结尾埋了一个名字

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那期视频发出去之后

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一位研究这种分子

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超过二十年的科学家

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给我发了一堆论文

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和她自己的亲身经历

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她是生物物理学博士

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曾在新加坡国立大学当了十一年助理教授

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现在在国科温州研究院缩醛磷脂项目公司做研发顾问

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她是那篇立方膜经典综述论文的共同作者

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也是国际缩醛磷脂学会的执行委员会成员

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她说

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缩醛磷脂是她追了二十多年的分子

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她管它叫立方膜衍生的缩醛磷脂

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哈喽

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大家好

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我是王利杰

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今天我们来深挖这个名字拗口但可能极其重要的分子

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缩醛磷脂

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你可能一辈子都没听过这四个字

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但你大脑里每五个磷脂分子当中

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就有一个是它

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先说它长什么样

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缩醛磷脂属于醚磷脂家族

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它的化学骨架跟普通磷脂几乎一模一样

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但有一个关键的不同

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在甘油骨架的一号位上

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普通磷脂用的是酯键

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而缩醛磷脂用的是一个乙烯基醚键

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就一个键的差别

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但就这一个键

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决定了它最核心的超能力

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抗氧化

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为什么

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因为乙烯基醚键天生就容易被自由基攻击

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自由基来了

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缩醛磷脂第一个冲上去

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用自己的乙烯醚键跟自由基反应

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把自己牺牲掉

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保护周围其他脂质分子不被氧化

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你可以把它想象成细胞膜上的活体防弹衣

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不是被动地挡子弹

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而是主动站出来替队友吃下那一枪

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但它的功能远不止这一个

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缩醛磷脂的二号位上通常连着一条多不饱和脂肪酸

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包括 DHA 和 EPA

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这些是什么

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是身体产生抗炎信号分子的原材料

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所以缩醛磷脂同时扮演两个角色

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一个是抗氧化卫兵

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一个是抗炎弹药库

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除此之外

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它还参与胆固醇代谢调节

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参与细胞膜上脂筏结构的组装

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参与膜融合和囊泡运输

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它是细胞膜世界里的多面手

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那它在人体里怎么分布

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大脑和心脏是两大重镇

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在大脑中

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缩醛磷脂占所有甘油磷脂的将近百分之三十

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在髓鞘里更夸张

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乙醇胺甘油磷脂中有百分之七十都是缩醛磷脂

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髓鞘是什么

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就是包裹神经纤维的那层绝缘层

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保证你的神经信号能高速传导而不短路

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心脏里浓度也很高

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免疫细胞中同样富集

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你发现规律了吗

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凡是膜功能需要高度活跃的地方

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缩醛磷脂就扎堆出现

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好

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接下来一个关键问题

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它是怎么被制造出来的

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缩醛磷脂的合成是一场跨越两个细胞器的接力赛

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前两步发生在过氧化物酶体里面

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后面几步在内质网完成

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总共七步反应

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过氧化物酶体

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这个名字你可能很少听到

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你知道线粒体是发电站

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但过氧化物酶体才是真正的化工厂

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它负责超长链脂肪酸的分解

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负责活性氧的清除

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还负责缩醛磷脂合成的起步

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你细胞膜上的防弹衣

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就是在这间化工厂里开始生产的

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而且这条产线有一个精妙的自我调节机制

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当膜上缩醛磷脂的浓度够了

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内质网的感受器会发信号回过氧化物酶体

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降低合成速度

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当缩醛磷脂被消耗掉了

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信号解除

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合成重新加速

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一个自我平衡的闭环

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那问题出在哪里

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出在衰老

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随着年龄增长

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过氧化物酶体的功能逐渐下降

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负责催化合成第一步的那个酶

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活性降低了

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原材料供应不足

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整条产线的产能开始下滑

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与此同时

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老化的细胞产生更多自由基

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消耗更多缩醛磷脂

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你看到这个局面了吗

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一边是工厂在老化

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产能在下降

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另一边是战场在扩大

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消耗在上升

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一条负螺旋就这样悄悄启动了

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缩醛磷脂少了

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膜的抗氧化防线崩了

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防线崩了

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更多脂质被氧化

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膜的精密结构开始退化

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我们之前在极小曲面那期讲过

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缩醛磷脂和立方膜结构是双向正反馈的关系

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结构稳定了分子

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分子保护了结构

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当分子不够了

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结构也撑不住了

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这条负螺旋一旦启动

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就很难靠身体自己刹车

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这不是理论推演

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这是真实的临床观察

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科学研究已经在多种疾病中

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发现了缩醛磷脂的显著下降

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而且不只是阿尔茨海默症

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帕金森病 多发性硬化

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甚至精神分裂症患者体内的

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缩醛磷脂水平都偏低

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这些疾病看起来天差地别

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但它们共享一个底层特征

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膜出了问题

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最典型的是阿尔茨海默症

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多项研究发现

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患者大脑和血液中的缩醛磷脂含量显著降低

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而且降低程度与认知损伤的严重性正相关

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美国拉什大学的记忆与衰老项目追踪了多年的数据

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发现一个令人震惊的规律

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一个八十五岁的老人

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如果血浆缩醛磷脂水平高

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患痴呆的概率只有百分之五

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而同样八十五岁

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缩醛磷脂水平低的

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概率飙升到百分之二十八

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同一个年龄

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风险相差五倍多

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二零二四年的一项研究

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创建了一种可诱导敲除

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缩醛磷脂合成基因的小鼠模型

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什么意思呢

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就是让成年小鼠的

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缩醛磷脂合成能力

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在某一天突然被人为关闭

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结果仅仅四个月

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这些小鼠就出现了行为异常和神经传导功能的改变

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这说明缩醛磷脂的下降不仅仅是衰老的副产品

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它本身就在驱动退行性变化

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二零二二年一项

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发表在 分子生物科学前沿 上的研究

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更直接

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研究者给十六个月大的老年小鼠

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连续补充缩醛磷脂两个月

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结果呢

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认知表现明显改善

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海马区的突触丧失得到缓解

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神经再生被激活了

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小胶质细胞的炎症反应也被抑制了

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缩醛磷脂在同一个实验里同时做到了三件事

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抗炎

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促突触再生

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改善认知

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但阿尔茨海默症还只是故事的一个面

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她发来的一篇二零二三年的

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综述论文提出了一个更大胆的假说

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这篇论文发表在 脑研究通报 上

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由她和加拿大维多利亚大学的特朗布莱博士共同通讯

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论文指出

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长新冠后遗症和慢性疲劳综合征

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这两种让无数人极度虚弱的疾病

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背后可能共享一个病理机制

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核心就是慢性炎症导致的神经胶质细胞功能障碍

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而缩醛磷脂缺乏在其中扮演关键角色

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逻辑链是这样的

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病毒感染或者严重的生理应激触发了急性免疫反应

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大脑中的小胶质细胞和星形胶质细胞被过度激活

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进入促炎状态

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正常情况下

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它们会在一段时间后回到平静

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但有些人的胶质细胞回不去了

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它们变成了慢性的低烈度炎症源

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这种持续的神经炎症大量消耗缩醛磷脂

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同时氧化应激又在破坏过氧化物酶体

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进一步压低合成能力

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于是你得到了一个跟衰老一模一样的负螺旋

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只不过这一次

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它被病毒感染提前触发了

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脑雾

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极度疲劳

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运动后症状加重

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这些长新冠和慢性疲劳综合征最典型的症状

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可能正是大脑膜系统

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在缩醛磷脂耗尽后

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发出的求救信号

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那到底能不能补

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这是所有人最关心的问题

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日本九州大学名誉教授藤野武彦

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是缩醛磷脂补充疗法的先驱

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他的团队在全世界首次成功

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从扇贝中高纯度提取了缩醛磷脂

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并开发了口服补充剂

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00:08:49,987 --> 00:08:51,155
二零一七年

218
00:08:51,228 --> 00:08:54,194
他主导了一项里程碑式的临床试验

219
00:08:54,588 --> 00:08:55,175
多中心

220
00:08:55,627 --> 00:08:56,055
随机

221
00:08:56,507 --> 00:08:56,935
双盲

222
00:08:57,348 --> 00:08:58,515
安慰剂对照

223
00:08:58,828 --> 00:08:59,854
三百二十八名

224
00:09:00,188 --> 00:09:02,114
六十到八十五岁的

225
00:09:02,147 --> 00:09:04,114
轻度阿尔茨海默症和

226
00:09:04,188 --> 00:09:06,915
轻度认知障碍患者参与实验

227
00:09:07,267 --> 00:09:11,275
每天口服一毫克扇贝来源的缩醛磷脂

228
00:09:11,387 --> 00:09:12,795
持续二十四周

229
00:09:13,318 --> 00:09:14,104
结果很有意思

230
00:09:14,397 --> 00:09:15,484
也很真实

231
00:09:15,677 --> 00:09:16,505
整体数据看

232
00:09:16,877 --> 00:09:18,436
治疗组和安慰剂组

233
00:09:18,438 --> 00:09:20,165
在主要评估指标上

234
00:09:20,198 --> 00:09:22,405
没有达到统计学显著差异

235
00:09:22,517 --> 00:09:23,844
但亚组分析中

236
00:09:23,877 --> 00:09:28,045
轻度阿尔茨海默症的女性患者和七十七岁以下的患者

237
00:09:28,078 --> 00:09:31,525
治疗组的记忆功能改善达到了统计学显著

238
00:09:31,797 --> 00:09:32,224
同时

239
00:09:32,478 --> 00:09:35,076
安慰剂组的血浆缩醛磷脂水平

240
00:09:35,078 --> 00:09:37,604
在二十四周内出现了明显下降

241
00:09:37,637 --> 00:09:39,364
而治疗组维持住了

242
00:09:39,677 --> 00:09:40,505
安全性方面

243
00:09:40,797 --> 00:09:43,354
没有发生严重不良事件

244
00:09:43,667 --> 00:09:44,575
这告诉我们什么

245
00:09:45,068 --> 00:09:46,134
口服缩醛磷脂

246
00:09:46,468 --> 00:09:48,186
至少在某些人群中

247
00:09:48,187 --> 00:09:50,435
展现了改善认知的信号

248
00:09:50,748 --> 00:09:52,795
但目前的证据还不够强

249
00:09:52,868 --> 00:09:54,834
不足以下确定性的结论

250
00:09:55,307 --> 00:09:56,906
二零二五年发表在

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00:09:56,907 --> 00:09:59,507
美国实验生物学学会会刊 上的

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00:09:59,507 --> 00:10:00,915
一篇综述指出

253
00:10:01,108 --> 00:10:03,714
剂量不足和生物利用度有限

254
00:10:03,787 --> 00:10:05,974
可能是限制临床效果的

255
00:10:06,147 --> 00:10:07,155
主要瓶颈

256
00:10:07,547 --> 00:10:09,267
每天一毫克的剂量

257
00:10:09,267 --> 00:10:12,594
对于整个大脑庞大的缩醛磷脂池来说

258
00:10:12,627 --> 00:10:14,276
确实太少了

259
00:10:14,510 --> 00:10:17,396
她在一篇2023年的公开评论中

260
00:10:17,429 --> 00:10:19,197
分享了她自己的选择

261
00:10:19,510 --> 00:10:23,756
她和母亲已经持续服用藤野教授的产品7到8年

262
00:10:23,990 --> 00:10:27,149
她自己感染新冠期间加倍剂量服用

263
00:10:27,150 --> 00:10:28,236
症状轻微

264
00:10:28,270 --> 00:10:28,776
恢复快

265
00:10:29,150 --> 00:10:31,396
没有出现任何长新冠症状

266
00:10:31,630 --> 00:10:33,789
她的一位患有自闭症的家人

267
00:10:33,789 --> 00:10:35,228
在服用六个月后

268
00:10:35,230 --> 00:10:36,837
也出现了明显改善

269
00:10:37,110 --> 00:10:39,557
她说的一句话让我印象很深

270
00:10:39,949 --> 00:10:40,297
她说

271
00:10:40,789 --> 00:10:42,337
缩醛磷脂不是药物

272
00:10:42,549 --> 00:10:43,549
是营养素

273
00:10:43,549 --> 00:10:43,977
安全

274
00:10:44,189 --> 00:10:45,197
而且有效

275
00:10:45,549 --> 00:10:48,337
人们总喜欢把事情搞复杂

276
00:10:48,610 --> 00:10:49,597
我必须说清楚

277
00:10:49,970 --> 00:10:51,489
这些是个人经历

278
00:10:51,490 --> 00:10:52,856
不是临床证据

279
00:10:52,970 --> 00:10:55,496
单个案例不能证明因果关系

280
00:10:55,850 --> 00:10:57,616
但她不是普通消费者

281
00:10:57,730 --> 00:11:00,537
她是这个领域深耕二十年的研究者

282
00:11:00,649 --> 00:11:04,496
发了三十多篇缩醛磷脂和立方膜相关的论文

283
00:11:04,850 --> 00:11:05,876
她的个人选择

284
00:11:06,169 --> 00:11:08,138
至少值得认真参考

285
00:11:08,451 --> 00:11:09,557
而且你注意到没有

286
00:11:10,171 --> 00:11:13,817
从藤野教授的临床试验到她个人的实践

287
00:11:13,890 --> 00:11:15,337
有一个共同的信号

288
00:11:15,850 --> 00:11:18,697
补充缩醛磷脂的安全性是非常高的

289
00:11:19,091 --> 00:11:20,597
三百多人的双盲试验

290
00:11:20,931 --> 00:11:22,018
二十四周

291
00:11:22,171 --> 00:11:23,778
零严重不良事件

292
00:11:24,250 --> 00:11:25,658
这其实也不奇怪

293
00:11:26,091 --> 00:11:29,457
缩醛磷脂本来就是你身体里天然存在的分子

294
00:11:29,770 --> 00:11:32,378
你不是在往身体里加一个外来的东西

295
00:11:32,650 --> 00:11:35,097
而是在补回一个正在流失的东西

296
00:11:35,411 --> 00:11:37,498
最后我想回到一个更大的问题

297
00:11:37,891 --> 00:11:40,338
我们可能需要重新理解大脑衰老

298
00:11:40,450 --> 00:11:42,657
它也许不是某个基因突变的问题

299
00:11:42,850 --> 00:11:45,137
不是某个蛋白质错误折叠的问题

300
00:11:45,291 --> 00:11:48,218
而是一场化学反应容器的缓慢坍塌

301
00:11:48,610 --> 00:11:51,578
当你的细胞膜失去了缩醛磷脂的保护

302
00:11:51,730 --> 00:11:55,137
所有本来运转良好的生化过程都开始走样

303
00:11:55,370 --> 00:11:56,817
不是软件出了错

304
00:11:56,891 --> 00:11:59,667
是硬件的物理形态维持不住了

305
00:11:59,899 --> 00:12:02,226
你可以闭上眼睛感受一下

306
00:12:02,499 --> 00:12:05,027
此刻你的大脑正在思考这句话

307
00:12:05,379 --> 00:12:07,427
这个思考之所以能发生

308
00:12:07,499 --> 00:12:10,547
是因为你有上千亿个突触在同时放电

309
00:12:10,659 --> 00:12:14,027
而每一次放电都需要囊泡穿过细胞膜

310
00:12:14,300 --> 00:12:16,946
膜的状态决定了信号传递的质量

311
00:12:17,180 --> 00:12:19,986
你觉得你脑子不如年轻时候好使了

312
00:12:20,019 --> 00:12:21,579
可能不是你变笨了

313
00:12:21,580 --> 00:12:23,544
而是你的膜变脆了

314
00:12:23,817 --> 00:12:27,144
上一次我们从几何学的角度理解了这件事

315
00:12:27,697 --> 00:12:30,585
极小曲面提供了膜的最优形态

316
00:12:31,138 --> 00:12:34,505
这一次我们从分子的角度理解了同一件事

317
00:12:34,857 --> 00:12:37,825
缩醛磷脂提供了膜的化学保护

318
00:12:38,418 --> 00:12:39,524
结构和分子

319
00:12:39,898 --> 00:12:41,304
几何和化学

320
00:12:41,337 --> 00:12:43,144
它们不是两个独立的故事

321
00:12:43,577 --> 00:12:45,781
它们是同一个故事的两面

322
00:12:46,293 --> 00:12:47,840
那这个故事有没有第三面

323
00:12:48,373 --> 00:12:51,561
能不能用合成生物学的方法大规模生产缩醛磷脂

324
00:12:52,013 --> 00:12:55,120
能不能用纳米颗粒包裹来提高它的生物利用度

325
00:12:55,614 --> 00:12:58,181
能不能用精准的脂质组学检测

326
00:12:58,214 --> 00:13:00,253
来评估每个人的缺乏程度

327
00:13:00,253 --> 00:13:01,281
然后定向补充

328
00:13:01,893 --> 00:13:04,580
这些问题都正在被认真地探索

329
00:13:05,149 --> 00:13:06,956
也许有一天你去体检

330
00:13:07,029 --> 00:13:08,589
除了查血糖血脂

331
00:13:08,590 --> 00:13:09,836
还会多查一项

332
00:13:10,310 --> 00:13:11,997
你的缩醛磷脂水平

333
00:13:12,487 --> 00:13:14,454
你觉得你的大脑是在衰老

334
00:13:14,568 --> 00:13:15,635
还是在失修

335
00:13:16,247 --> 00:13:17,355
如果答案是失修

336
00:13:17,768 --> 00:13:19,135
那修补它的材料

337
00:13:19,207 --> 00:13:21,547
也许就藏在一只扇贝里面

338
00:13:21,901 --> 00:13:22,568
我是王利杰

339
00:13:22,741 --> 00:13:23,787
我们下期见