Science:打破固有认知!Science揭秘肠道运行新机制:合成胆固醇中的“好学生”,或为肝脏疾病治疗带来新靶点

2021-08-03 生物探索 生物探索

这一特殊的高密度脂蛋白将为营养性、酒精性或外科手术造成的肝脏损害提供更多的预防或治疗途径。

胆固醇,大家都很熟悉,经常有人将其归类为有害身体健康的“坏东西”,“降低胆固醇”也是时常萦绕在大家耳边的一句话。然而,很多人似乎会忘记,胆固醇也有“好”“坏”之分,“坏”胆固醇,叫做低密度脂蛋白(LDL-C),它经常会对心脏、动脉等造成伤害,而“好”胆固醇,叫做高密度脂蛋白(HDL-C),能够清洁疏通动脉,具有抗炎、抗氧化、预防冠心病的作用。

而这种“好”胆固醇,可能比我们了解到的好处还要多。近日,华盛顿大学医学院的研究团队在 Science 发表最新研究 Enterically derived high-density lipoprotein restrains liver injury through the portal vein,该项研究指出,人体的肝脏承担了在血液中产生与合成大部分高密度脂蛋白的角色,但类似的合成也发生在肠道。研究人员在小肠内发现了一种特殊类型的高密度脂蛋白HDL?,它以HDL的亚种形式存在,会与肠道内的脂多糖炎症分子结合,阻断引起肝脏炎症的细菌信号,以达到保护肝脏的目的。

由于高密度脂蛋白无法直接从肠道转移到肝脏,因此,该研究首先对HDL的运作机制进行了探究。高密度脂蛋白的合成需要载脂蛋白apoA1和胆固醇转运蛋白ABCA1的参与,研究人员在小鼠体内使用了光激活绿色荧光蛋白对高密度脂蛋白进行了标记,用来追踪HDL的合成与转移过程。他们发现,门静脉是HDL?转移过程发生的重要场所,HDL会首先从肠道进入门静脉,接着通过肝脏,从肝脏进入体循环,从而分散在淋巴中。

HDL运作机制

接着,研究人员对HDL?在肠道中的水平与治疗肝脏疾病的关系进行了研究。此前的研究显示,任何一种肠道损伤都会影响革兰氏阴性细菌对人体的作用,这种细菌所产生的脂多糖炎症分子(LPS)会通过门静脉进入肝脏,激活引发炎症的巨噬细胞等免疫细胞,从而导致包括脂肪肝、肝纤维化在内的肝脏疾病的发作。

在该项研究中,研究人员发现,HDL在进入门静脉后,会与脂多糖结合蛋白(LBP)共同结合LPS,当这种有害的脂多糖与HDL和LBP的复合物结合时,将会抑制一种被称为Kupffer细胞(KC)的免疫细胞的激活,阻断LPS与其受体TLR4的结合,从而保护肝脏免受炎症的干扰。

HDL与LPS相结合以阻止LPS与TLR4受体的结合

得出结论后,研究人员继续加深对HDL的探索。他们建立了一个促进明显肝纤维化的小鼠小肠切除模型,切除了小鼠50%或75%的小肠,保留了小肠近端和回肠末端,以探究HDL?这种肠源性高密度脂蛋白被破坏后对肝脏损伤的影响。试验结论显示,当切除小肠近端50%或远端50%的部分时,门静脉血中的HDL-C含量均呈下降趋势,尤其是远端切除后,门静脉血中HDL-C的下降幅度更大,而由于有较低的HDL-C与LPS进行结合,LPS活性增加,随之而来的,是这些小鼠表现出更加严重的肝损伤、纤维化和炎症。

以上试验结果表明,较短的肠道意味着能够产生的HDL较少,而手术本身会导致肠道的损伤状态,从而使更多的LPS溢出到门静脉血中,造成肝脏的炎症发作。同时,若切除肠道中产生最多HDL?的部分时,其肝脏损伤就会最严重。研究人员同时加入了高脂肪饮食和酒精性肝病的小鼠模型,以观察相同的影响是否还会发生,所有肠损伤模型都验证了HDL?的保护作用。

小鼠小肠切除模型中HDL对肝脏损伤的影响

研究人员进一步表明,人类血液样本中也存在相同的保护性分子复合物,这说明人类存在着类似的保护机制。他们还使用LXR激动剂来增加小鼠肠道中的HDL?,发现它对不同类型的肝损伤均有保护作用。虽然这种药物只能用于动物研究,但也揭示了治疗或预防肝病的新可能性。

目前,该研究还处在小鼠阶段,同时仍有很多问题悬而未决,但是HDL?对肝脏的保护作用是值得肯定的,这一特殊的高密度脂蛋白将为营养性、酒精性或外科手术造成的肝脏损害提供更多的预防或治疗途径。该研究的作者之一Gwendalyn J. Randolph表示:“我们希望HDL能成为未来肝病治疗的靶点,我们的研究正在继续,以便更好地探究这一独特护肝过程的细节。”

原始出处:

Yong-Hyun Han, et al. Enterically derived high-density lipoprotein restrains liver injury through the portal vein. Science 23 Jul 2021:Vol. 373, Issue 6553, eabe6729. DOI: 10.1126/science.abe6729.

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1982802, encodeId=9b8e1982802ad, content=<a href='/topic/show?id=89c4e06902e' target=_blank style='color:#2F92EE;'>#疾病治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70690, encryptionId=89c4e06902e, topicName=疾病治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d64f419, createdName=qindq, createdTime=Sat Oct 23 08:06:54 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1253394, encodeId=1ae912533949d, content=<a href='/topic/show?id=12c98145216' target=_blank style='color:#2F92EE;'>#肝脏疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81452, encryptionId=12c98145216, topicName=肝脏疾病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87531, createdName=klivis, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288324, encodeId=f257128832423, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376331, encodeId=b42f13e6331be, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039448, encodeId=4063103944838, content=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, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Tue Aug 03 19:06:54 CST 2021, time=2021-08-03, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1982802, encodeId=9b8e1982802ad, content=<a href='/topic/show?id=89c4e06902e' target=_blank style='color:#2F92EE;'>#疾病治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70690, encryptionId=89c4e06902e, topicName=疾病治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d64f419, createdName=qindq, createdTime=Sat Oct 23 08:06:54 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1253394, encodeId=1ae912533949d, content=<a href='/topic/show?id=12c98145216' target=_blank style='color:#2F92EE;'>#肝脏疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81452, encryptionId=12c98145216, topicName=肝脏疾病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87531, createdName=klivis, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288324, encodeId=f257128832423, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376331, encodeId=b42f13e6331be, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039448, encodeId=4063103944838, content=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, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Tue Aug 03 19:06:54 CST 2021, time=2021-08-03, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=1982802, encodeId=9b8e1982802ad, content=<a href='/topic/show?id=89c4e06902e' target=_blank style='color:#2F92EE;'>#疾病治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70690, encryptionId=89c4e06902e, topicName=疾病治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d64f419, createdName=qindq, createdTime=Sat Oct 23 08:06:54 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1253394, encodeId=1ae912533949d, content=<a href='/topic/show?id=12c98145216' target=_blank style='color:#2F92EE;'>#肝脏疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81452, encryptionId=12c98145216, topicName=肝脏疾病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87531, createdName=klivis, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288324, encodeId=f257128832423, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376331, encodeId=b42f13e6331be, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039448, encodeId=4063103944838, content=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, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Tue Aug 03 19:06:54 CST 2021, time=2021-08-03, status=1, ipAttribution=)]
    2021-08-05 lsndxfj
  4. [GetPortalCommentsPageByObjectIdResponse(id=1982802, encodeId=9b8e1982802ad, content=<a href='/topic/show?id=89c4e06902e' target=_blank style='color:#2F92EE;'>#疾病治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70690, encryptionId=89c4e06902e, topicName=疾病治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d64f419, createdName=qindq, createdTime=Sat Oct 23 08:06:54 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1253394, encodeId=1ae912533949d, content=<a href='/topic/show?id=12c98145216' target=_blank style='color:#2F92EE;'>#肝脏疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81452, encryptionId=12c98145216, topicName=肝脏疾病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87531, createdName=klivis, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288324, encodeId=f257128832423, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376331, encodeId=b42f13e6331be, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039448, encodeId=4063103944838, content=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, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Tue Aug 03 19:06:54 CST 2021, time=2021-08-03, status=1, ipAttribution=)]
    2021-08-05 jichang
  5. [GetPortalCommentsPageByObjectIdResponse(id=1982802, encodeId=9b8e1982802ad, content=<a href='/topic/show?id=89c4e06902e' target=_blank style='color:#2F92EE;'>#疾病治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70690, encryptionId=89c4e06902e, topicName=疾病治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d64f419, createdName=qindq, createdTime=Sat Oct 23 08:06:54 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1253394, encodeId=1ae912533949d, content=<a href='/topic/show?id=12c98145216' target=_blank style='color:#2F92EE;'>#肝脏疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81452, encryptionId=12c98145216, topicName=肝脏疾病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87531, createdName=klivis, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288324, encodeId=f257128832423, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376331, encodeId=b42f13e6331be, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 05 07:06:54 CST 2021, time=2021-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039448, encodeId=4063103944838, content=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, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Tue Aug 03 19:06:54 CST 2021, time=2021-08-03, status=1, ipAttribution=)]
    2021-08-03 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

相关资讯

JACC发布高甘油三酯血症患者降低ASCVD风险的临床指南

在患者使用降脂药物之前和期间,生活方式的干预,包括坚持心脏健康的饮食、定期体育锻炼、避免烟草制品、限制饮酒和保持健康体重,仍然是降低ASCVD风险的重要组成部分

BMJ子刊:别让糖尿病伤了你的肾!糖尿病肾病发病率变高

全世界有高达4.51亿的成年人患有糖尿病(DM)。到2045年,这一数字将上升到6.93亿成年人。

梅斯心血管疾病进展(001期)

枸杞可以增强健康饮食方式对心血管的保护作用

近200万人的大型研究分析:多喝牛奶会增加心脏代谢风险吗?

牛奶富含蛋白质、钙、脂肪和多种微量元素,是我们膳食中重要的营养来源。

新研究:跳舞或改善绝经女性的健康,提高自尊

每周三次的舞蹈课,可以改善绝经后妇女的健身和代谢状况,自我形象和自尊心。除了这些好处之外,妇女们还可能从学习新事物的经历中建立一种友谊。

天舟2号发射延迟,限时禁食会影响后代健康:一周科技导读

近日,《英国皇家学会学报B》(Proceedings of the Royal Society)的一篇论文中,研究小组调查了限时禁食对线虫及其三代后代的寿命和繁殖的影响。