PNAS:戒烟者福音!二甲双胍或成为尼古丁戒断综合征的克星!

2018-04-14 Ruthy,Yui 转化医学网

众所周知,吸烟有害健康。经常吸烟的人,却享受不到大自然的恩惠,吸入的不是新鲜空气,而是被烟雾污染的有毒气体,许多深受其害者走上了戒烟之路,但是单纯靠毅力戒烟成功者却寥寥无几,罪魁祸首就是“尼古丁戒断综合征”!科学家们针对这一戒断症状开展了大量研究,近期有研究发现AMPK通路激活剂-二甲双胍或是成为尼古丁戒断综合征的克星,这或可成为戒烟者的福音!

众所周知,吸烟有害健康。经常吸烟的人,却享受不到大自然的恩惠,吸入的不是新鲜空气,而是被烟雾污染的有毒气体,许多深受其害者走上了戒烟之路,但是单纯靠毅力戒烟成功者却寥寥无几,罪魁祸首就是“尼古丁戒断综合征”!科学家们针对这一戒断症状开展了大量研究,近期有研究发现AMPK通路激活剂-二甲双胍或是成为尼古丁戒断综合征的克星,这或可成为戒烟者的福音!

研究发现,当人吸烟时,香烟中的尼古丁瞬间就能进入血液,使大脑内神经系统产生一种快乐激素,它能够缓解人紧张、抑郁、烦躁等精神状态,人体持续长期的摄入尼古丁,大脑内神经系统会逐渐对尼古丁的刺激产生依赖,这就是吸烟者对香烟上瘾的主要原因,也是香烟难以戒断的根本原因。

“尼古丁戒断综合症”是戒烟者的身体因为突然缺失尼古丁导致内循环和内分泌失衡,出现易怒、心烦、焦虑、急躁、心慌、注意力无法集中的症状,严重的还会出现关节疼痛、肠胃不适,这些痛苦使很多人无法坚持下去,极少数人是靠毅力戒了烟,但也很容易复吸。

我们知道,AMP依赖的蛋白激酶(AMPK)是能量平衡的主要调节剂,可受细胞中的应激物刺激而被激活。近期,来自宾法尼亚大学的Julia K. Brynildsen等人发现AMPK通路的激活有助于消除尼古丁戒断作用,研究人员由此推断在药理学上增加pAMPK水平或可减少尼古丁的戒断症状。

他们对小鼠进行AMPK激活剂-二甲双胍刺激后,发现尼古丁戒断症状减少,进一步的研究这是因为海马中存在AMPK蛋白,据此他们提出AMPK激活剂或可成为戒烟的新方法。该研究以《Activation of AMPK by metformin improves withdrawal signs precipitated by nicotine withdrawal》为题发表在近期的《PNAS》上。

一直以来,多数研究仅确定了AMPK在外周组织中的作用,但其在中枢神经系统中的作用尚未得到充分认证。近期有研究表明,AMPK信号与消极的认知和行为有关,而这些认知和行为与尼古丁戒断期间烟瘾的复发息息相关。

因此,研究人员试图确定在尼古丁戒断期间控制AMPK活性是否可以改善尼古丁戒断的情感症状。他们使用AMPK变构激活剂5-氨基咪唑-4-甲酰胺核糖核苷酸(AICAR)对尼古丁戒断期间的小鼠进行实验,他们发现AICAR可引起海马中AMPK通路的显着激活,之后小鼠焦虑样行为得到缓解,一段时间后AICAR完全消除了尼古丁戒断的影响。这说明AMPK通路的激活有助于消除尼古丁戒断作用。


AICAR消除尼古丁戒断后的焦虑样行为

之后研究人员使用二甲双胍处理了尼古丁戒断期间的小鼠,发现全身二甲双胍预处理一周后小鼠海马中的pAMPK增加,AMPK通路激活。另外,二甲双胍还在完全不影响体重、食物消耗和血液葡萄糖水平的前提下消除了尼古丁戒断引起的焦虑样行为。而且,AICAR和二甲双胍均降低了幼稚小鼠食欲不振的潜伏期,这表明AMPK的激活可能为一般抗焦虑以及尼古丁戒断引起的焦虑提供新的治疗方法。


全身使用二甲双胍可增加海马pAMPK,并且减少尼古丁戒断期间的焦虑样行为

我们知道,二甲双胍有多个外周靶标,为了确定二甲双胍是否真的改善尼古丁戒断症状,而非仅起外周效应,研究人员将与渗透性小型泵相连的插管植入到小鼠脑室内,集中递送二甲双胍(50μg/ d)或盐水(对照)1周。

他们发现二甲双胍在海马中引起AMPK激活,而在肝脏中却没有这种现象,而且海马中的二甲双胍完全阻断了尼古丁戒断引起的焦虑样行为。为了证实海马中的AMPK是二甲双胍介导的尼古丁戒断后焦虑样行为减少的相关靶点,研究人员将含有条件性等位基因Ampkα1loxP/ loxP的两个α亚基注射到小鼠的背侧和腹侧海马中,并使AMPKα的位点特异性缺失,蛋白质轨迹分析证实了AMPKαloxP/ loxP小鼠注射8周后,海马AMPKα总水平降低,但其他脑区(如皮层)则保持不变。此外,海马中的磷酸乙酰CoA羧化酶(pACC)的水平也出现降低,这证明了途径中出现了功能性缺失,这证实了AMPK是二甲双胍介导的尼古丁戒断后焦虑样行为减少的相关靶点。


脑室内注射二甲双胍激活了海马AMPK通路并减少尼古丁戒断症状


二甲双胍在尼古丁戒断期间的抗焦虑作用与海马中AMPKα有关

这项研究结果证明了二甲双胍能够通过激活海马中的AMPK通路缓解尼古丁戒断后产生的焦虑样行为,可以用作尼古丁戒断治疗的新型药物,同时二甲双胍还有具有良好的糖尿病治疗安全性,因此应该鼓励研究人员将这些发现转化为未来的临床试验,以提高吸烟者的持续戒烟率,并使血糖正常化。

原始出处:

Brynildsen JK,et al.Activation of AMPK by metformin improves withdrawal signs precipitated by nicotine withdrawal.Proc Natl Acad Sci U S A. 2018 Apr 2. pii: 201707047.

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    2018-08-06 drwjr
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    2018-04-25 12268205m49暂无昵称

    学习了

    0

  4. 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Sat Apr 14 21:57:13 CST 2018, time=2018-04-14, status=1, ipAttribution=)]
    2018-04-18 wxl882001

    学习一下

    0

  5. 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createdBy=c3da1990174, createdName=yfjms, createdTime=Wed Apr 18 07:26:12 CST 2018, time=2018-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=306498, encodeId=3590306498eb, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Tue Apr 17 05:38:23 CST 2018, time=2018-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431185, encodeId=d26914311853e, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Sat Apr 14 21:57:13 CST 2018, time=2018-04-14, status=1, ipAttribution=)]
    2018-04-18 吴匡靖

    ****你还有什么是不能的

    0

  6. 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createdBy=c3da1990174, createdName=yfjms, createdTime=Wed Apr 18 07:26:12 CST 2018, time=2018-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=306498, encodeId=3590306498eb, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Tue Apr 17 05:38:23 CST 2018, time=2018-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431185, encodeId=d26914311853e, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Sat Apr 14 21:57:13 CST 2018, time=2018-04-14, status=1, ipAttribution=)]
    2018-04-18 yfjms

    学习

    0

  7. 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createdBy=c3da1990174, createdName=yfjms, createdTime=Wed Apr 18 07:26:12 CST 2018, time=2018-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=306498, encodeId=3590306498eb, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Tue Apr 17 05:38:23 CST 2018, time=2018-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431185, encodeId=d26914311853e, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Sat Apr 14 21:57:13 CST 2018, time=2018-04-14, status=1, ipAttribution=)]
    2018-04-17 121832a9m88暂无昵称

    学习了

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1856160, encodeId=5469185616046, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Mon Aug 06 13:11:00 CST 2018, time=2018-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1992588, encodeId=5c5f19925887b, content=<a href='/topic/show?id=224054126c9' target=_blank style='color:#2F92EE;'>#戒断综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54126, encryptionId=224054126c9, topicName=戒断综合征)], attachment=null, authenticateStatus=null, 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createdBy=c3da1990174, createdName=yfjms, createdTime=Wed Apr 18 07:26:12 CST 2018, time=2018-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=306498, encodeId=3590306498eb, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Tue Apr 17 05:38:23 CST 2018, time=2018-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431185, encodeId=d26914311853e, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Sat Apr 14 21:57:13 CST 2018, time=2018-04-14, status=1, ipAttribution=)]
  9. [GetPortalCommentsPageByObjectIdResponse(id=1856160, encodeId=5469185616046, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Mon Aug 06 13:11:00 CST 2018, time=2018-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1992588, encodeId=5c5f19925887b, content=<a href='/topic/show?id=224054126c9' target=_blank style='color:#2F92EE;'>#戒断综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54126, encryptionId=224054126c9, topicName=戒断综合征)], attachment=null, authenticateStatus=null, 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createdBy=c3da1990174, createdName=yfjms, createdTime=Wed Apr 18 07:26:12 CST 2018, time=2018-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=306498, encodeId=3590306498eb, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Tue Apr 17 05:38:23 CST 2018, time=2018-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431185, encodeId=d26914311853e, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Sat Apr 14 21:57:13 CST 2018, time=2018-04-14, status=1, ipAttribution=)]
    2018-04-15 1222becem95暂无昵称

    学习了

    0

  10. 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Sat Apr 14 21:57:13 CST 2018, time=2018-04-14, status=1, ipAttribution=)]
    2018-04-14 王秀

    学习了.涨知识了!

    0

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Diabetes Obes Metab:二甲双胍升级为速释 服用方便是否会牺牲有效性安全性?

近期,《Diabetes Obes Metab》上的一项国际随机双盲研究(NCT01864174)比较了缓释(XR)二甲双胍和速释(IR)二甲双胍在2型糖尿病患者中的有效性和安全性。

二甲双胍减肥靠谱吗?

作为降糖药里的“老大哥”,二甲双胍近些年有些被推向神坛的趋势,陆续有研究称其可延长寿命、抗癌、减重等等,其减重作用受到了诸多关注。据了解有相当一部分人都有使用二甲双胍减肥的经历,其中不乏血糖正常的人群,那么使用二甲双胍减肥,究竟靠谱吗?

病例:二甲双胍是神药,但也可能导致严重并发症

   今天分享的是一例酸中毒的病例。   患者为一70岁男性,体重77 kg,体质指数28.3 kg/m²,患有2型糖尿病合并糖尿病肾病,冠心病, NYHA心功能III级充血性心力衰竭,中度原发性高血压(2期),肾功能不全。长期服药治疗,药物治疗方案:单硝酸异山梨酯60 mg qd,呋塞米40 mg qd,喹那普利20 mg qd,二甲双胍850 m

JAMA Pediatr:严重肥胖的II型糖尿病青少年患者减肥手术对血糖的控制效果优于药物治疗

研究认为,对于严重肥胖的II型糖尿病青少年患者,减肥手术对控制血糖、降低体重以及其他并发症的预防效果优于药物治疗

新研究确定二甲双胍又一大作用,除治疗糖尿病,还有这种附加好处

根据芝加哥的一份调查显示,不孕症,肥胖症和多囊卵巢综合征患者在使用低剂量利拉鲁肽与二甲双胍联合治疗的情况下,累积妊娠率增大。

BMJ:印度糖尿病药物引争议,五种二甲双胍组合存在待解决问题

马萨诸塞大学阿默斯特分校以及来自英国的研究人员们证实二甲双胍固定剂量组合的世界卫生组织指导方针(FDC)评估以及最畅销的印度糖尿病药物的安全和疗效。