Cell Stem Cell:揭示二甲双胍护胃机制!科学家发现二甲双胍可调节胃干细胞代谢,促进干细胞转化为分泌胃酸的细胞来护胃

2020-04-30 奇点糕 奇点网

这次神药被发掘出的效果,是对抗中国人健康的大敌——胃癌。

这次神药被发掘出的效果,是对抗中国人健康的大敌——胃癌。近期发表在Cell Stem Cell上,一项来自圣路易斯华盛顿大学的最新研究显示,二甲双胍可以调节胃内干细胞的代谢,促使它们分化为产胃酸的胃壁细胞(Parietal Cell)。

要想防范幽门螺杆菌这个胃癌最大的致癌因素,胃壁细胞分泌的适量胃酸必不可少,所以二甲双胍通过这条通路,起到了护胃的效果,这可能解释了服用二甲双胍与胃癌风险有关,以及神药的一些胃肠道副作用。

主要结论一目了然

其实早就有研究指出,服用二甲双胍的糖尿病患者胃癌风险低,毕竟吃神药的人真的是够多,数据好找。而去年香港大学团队的一项新分析显示,如果在根除幽门螺杆菌感染后才开始吃二甲双胍,就与胃癌风险下降51%有关了。

这么大的风险下降幅度,几乎是超越了以往所有同类研究的数据,那就很有深究的必要了。而开展本次研究的圣路易斯华盛顿大学团队,想到的是胃里的干细胞。

胃癌到底是不是起源于干细胞,在医学科研里争议非常大,但干细胞通过分化成各种不同的细胞,对胃粘膜上皮稳定的维持作用,肯定是和胃癌关系密切。不过干细胞的这种行为,肯定也会受到许多因素的影响,这其中就包括了代谢。

而二甲双胍的本职工作是什么?就是调节代谢嘛。如果二甲双胍对胃内的干细胞“惩强扶弱”,支持干细胞分化出更多保护胃的细胞,就能很好地解释护胃效果。

胃里面的细胞其实也很复杂哈(图片来源:Biomedicines)

怎么去验证这个假想呢?第一步是把那些保护胃的细胞挑出来,看看它们的基因表达,有没有体现与二甲双胍调控有关的转录改变,比如经典的AMPK代谢通路。

研究团队分析的目标,是胃内的胃壁细胞,它们在正常情况下分泌胃酸,从而抑制幽门螺杆菌的感染。结合前面香港大学的发现,如果二甲双胍能够给胃壁细胞撑腰,那么逻辑链就被串起来了,这个猜想也很快被转录表达分析证实。

接下来,研究团队让小鼠服用了两个星期的二甲双胍,发现胃壁细胞的数量会迅速上升,即使用他莫昔芬处理,杀死绝大多数的胃壁细胞后,二甲双胍也能促进干细胞分化成胃壁细胞,使胃壁细胞数量迅速恢复。

如果计算增长率的话,在二甲双胍激活AMPK的推动下,干细胞分化成胃壁细胞的速度会增加接近一倍,而且胃壁细胞的存活时间也明显延长,“神药”就这样双管齐下,起到了护胃效果。

注意圈出的部分,对比一下差距

在类器官上的进一步实验,也证实了二甲双胍增加胃壁细胞数量,促进这些细胞成熟的效果,而且二甲双胍还能抑制胃上皮祖细胞的增殖。这种调节效果,主要与AMPK通路激活的下游转录因子Klf4和PGC1α有关。

用研究团队在论文中的话说,这项研究首次证实了代谢通路可以在体内控上皮细胞的分化和成熟,而且胃壁细胞的大量受损,是胃癌发生的重要一步,二甲双胍就能防患于未然。

原始出处:Miao Z-F, Adkins-Threats M, Burclaff J R, et al. A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation [J]. Cell Stem Cell, 2020.4

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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Thu Apr 30 06:02:50 CST 2020, time=2020-04-30, status=1, ipAttribution=)]
    2020-05-03 独孤立克

    干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦

    0

  7. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Thu Apr 30 06:02:50 CST 2020, time=2020-04-30, status=1, ipAttribution=)]
    2020-04-30 肿肿

    机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要

    0

  10. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Thu Apr 30 06:02:50 CST 2020, time=2020-04-30, status=1, ipAttribution=)]
    2020-04-30 misszhang

    二甲双胍,神药!

    0

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