ATVB:全面认识肺动脉高压中肠-肠系膜-肺轴

2022-03-28 刘少飞 MedSci原创

肺动脉高压(PAH)期间的肠道-肠道-肺轴,特别关注寄生虫引起的PAH(Sch-PAH),并试图勾勒出病原体转位可能有助于慢性肺血管疾病发病的机制。

肺动脉高压(PAH)是一种威胁生命的疾病,其特征是血管细胞的过度增殖,包括平滑肌和内皮细胞。增殖过度的细胞最终会阻塞肺部血管,导致不可逆转的病变,共同推动肺部压力达到威胁生命的水平。尽管PAH的主要原因还不完全清楚,但一些研究表明它是由慢性肺部炎症引起的,如在病原体感染时观察到的。

奇怪的是,血管内寄生虫曼氏血吸虫的感染再现了导致慢性PAH发展的广泛的肺部炎症的几个方面。在全球范围内,目前有超过2亿人被血吸虫感染,其中约有5%的人因寄生虫卵诱导的肺部血管湮灭和重塑而患上AH(Sch-PAH)。在进入肺部之前,血吸虫卵在肠系膜静脉内释放,在那里它们或者穿过肠壁,干扰肠道微生物群,或者迁移到其他器官,包括肺和肝脏,增加压力。通过侧支循环的自发或手术肝脏旁路可以缓解门静脉系统的压力;然而,它也允许病原体、毒素和抗原转入肺部,最终导致多发性硬化。这篇简短概述了PAH期间的肠道-肠道-肺轴,特别关注Sch-PAH,并试图勾勒出病原体易位可能导致慢性肺血管疾病发病的机制。

肠道微生物组及对肺部健康的影响

肠道微生物组的一般方面人类的胃肠道被各种微生物定植,包括真菌、病毒和细菌,主要属于韧皮菌门、拟杆菌门、变形杆菌门、放线菌门、软骨菌门和蓝藻门。 这些微生物与宿主细胞有共生关系,对维持胃肠道和整个身体的平衡有很大贡献,而这些群落的破坏(即菌群失调)与局部和全身炎症性疾病的发展有关,包括自身免疫性疾病、癌症和肺部病症。总的来说,肠道微生物群、环境抗原和人类细胞之间的微调互动。病原体转位和慢性肺部炎症性疾病。 肠道菌群失调和肠系膜炎症对肺动脉高压的影响。以血吸虫病为模型研究病原体转位和肺部微生物组失调。

图1.影响肠道和肺部微生物组组成的内在和外在因素。人类的肠道和肺部微生物组(或生态系统)是在发育过程中形成的,它们的组成多年来显著依赖于内在和外在的宿主因素,包括被其他病原体感染。

图2.通过肠系膜连接肠道和肺部:一个研究不多的十字路口。为了应对胃肠道(GI)通透性的增加(肠漏),一些机会主义微生物,比其他共生微生物(包括大肠杆菌)更有效地进行易位,积累到腹腔、肠系膜淋巴结内,或达到系统循环,引起多器官疾病。淋巴系统在病原体、其分子和毒素进入其他器官(如肺)的生理和病理转移中占有重要地位;然而,肠系膜循环通过其分支进入门静脉系统并随后进入腔静脉和肺血管,提供了一条重要的肠道-肺沟通途径。自发的或手术的肠系膜分流可以使肠肺直接沟通,绕过肝脏清除。在有机体间和谐的相互作用下,组织的平衡性得以保存。然而,在不和谐的相互作用下,如在血吸虫病的慢性阶段,宿主就会屈服于疾病。

图3.血吸虫病相关PAH(Sch-PAH)中的肠道-肠道-肺轴。长期感染的个体在其肠系膜系统中寄生了成年血吸虫,这些血吸虫会产下成千上万的卵。曼氏血吸虫成虫和虫卵与肠系膜内皮细胞的相互作用,通过减少eNOS(内皮表达一氧化氮[NO]合成酶)和嘌呤受体P2X7R(嘌呤受体X7)的表达和功能,以及通过增加ADP诱导的P2YR1的激活和白细胞粘附和转入腹腔(右下框),促进内皮功能紊乱。一旦释放,一半的卵子会主动穿过肠壁,在肠壁和腹腔引起明显的炎症反应,促使微生物群失调和血管生成(左下角方框)。剩余的卵子分配到其他器官,包括肝脏,在那里它们可以阻碍窦状血管,导致严重的炎症和门静脉高压的发展。为了应对门静脉压力的升高,门静脉和中静脉侧支循环的形成不仅可以绕过肝脏,还可以使曼氏综合症的虫卵、抗原和毒素转入肺部。虽然很罕见,但也可能发生自发的侧支循环的形成(左上角方框)。虫卵从肠系膜转入肺部导致肺血管的阻塞、炎症重塑和Sch-PAH的发展,由于其转变为肌成纤维细胞或间质样细胞,表现为异常的内皮增生。与BMPRII(骨形态发生蛋白受体2)、Cav-1(穴居蛋白-1)和NO的表达减少以及TGF(转化生长因子)-β和TLR4(收费类受体4)/CD14介导的信号通路的升高有关(右上框)。

 

参考文献:

Oliveira SD. Insights on the Gut-Mesentery-Lung Axis in Pulmonary Arterial Hypertension: A Poorly Investigated Crossroad. Arterioscler Thromb Vasc Biol. 2022 Mar 17:ATVBAHA121316236. doi: 10.1161/ATVBAHA.121.316236. Epub ahead of print. PMID: 35296152.

 

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    2022-12-21 gongliu
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    2022-03-28 yangchou

    好文章,值得一读。

    1

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  4. [GetPortalCommentsPageByObjectIdResponse(id=1978002, encodeId=f85919e800240, content=<a href='/topic/show?id=20411e958de' target=_blank style='color:#2F92EE;'>#TVB#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17958, encryptionId=20411e958de, topicName=TVB)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1a5a149, createdName=gongliu, createdTime=Wed Dec 21 11:46:03 CST 2022, time=2022-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925578, encodeId=5bce19255e84b, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Aug 24 20:46:03 CST 2022, time=2022-08-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1206678, encodeId=bc0c12066e84b, content=好文章,值得一读。, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Mon Mar 28 19:04:54 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1206706, encodeId=5c511206e068c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Mon Mar 28 20:51:41 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207028, encodeId=a940120e02876, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Tue Mar 29 21:42:39 CST 2022, time=2022-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207684, encodeId=3236120e684fe, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Thu Mar 31 22:16:25 CST 2022, time=2022-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557276, encodeId=fae6155e27678, content=<a href='/topic/show?id=d5e281610db' target=_blank style='color:#2F92EE;'>#肠系膜#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81610, encryptionId=d5e281610db, topicName=肠系膜)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f84f14890130, createdName=zzc2216, createdTime=Mon Mar 21 09:46:03 CST 2022, time=2022-03-21, status=1, ipAttribution=)]
    2022-03-28 屋顶瞄爱赏月

    学习了

    1

    展开1条回复
  5. [GetPortalCommentsPageByObjectIdResponse(id=1978002, encodeId=f85919e800240, content=<a href='/topic/show?id=20411e958de' target=_blank style='color:#2F92EE;'>#TVB#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17958, encryptionId=20411e958de, topicName=TVB)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1a5a149, createdName=gongliu, createdTime=Wed Dec 21 11:46:03 CST 2022, time=2022-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925578, encodeId=5bce19255e84b, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Aug 24 20:46:03 CST 2022, time=2022-08-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1206678, encodeId=bc0c12066e84b, content=好文章,值得一读。, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Mon Mar 28 19:04:54 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1206706, encodeId=5c511206e068c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Mon Mar 28 20:51:41 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207028, encodeId=a940120e02876, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Tue Mar 29 21:42:39 CST 2022, time=2022-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207684, encodeId=3236120e684fe, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Thu Mar 31 22:16:25 CST 2022, time=2022-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557276, encodeId=fae6155e27678, content=<a href='/topic/show?id=d5e281610db' target=_blank style='color:#2F92EE;'>#肠系膜#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81610, encryptionId=d5e281610db, topicName=肠系膜)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f84f14890130, createdName=zzc2216, createdTime=Mon Mar 21 09:46:03 CST 2022, time=2022-03-21, status=1, ipAttribution=)]
    2022-03-29 杨海东

    学习

    1

    展开1条回复
  6. [GetPortalCommentsPageByObjectIdResponse(id=1978002, encodeId=f85919e800240, content=<a href='/topic/show?id=20411e958de' target=_blank style='color:#2F92EE;'>#TVB#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17958, encryptionId=20411e958de, topicName=TVB)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1a5a149, createdName=gongliu, createdTime=Wed Dec 21 11:46:03 CST 2022, time=2022-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925578, encodeId=5bce19255e84b, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Aug 24 20:46:03 CST 2022, time=2022-08-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1206678, encodeId=bc0c12066e84b, content=好文章,值得一读。, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Mon Mar 28 19:04:54 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1206706, encodeId=5c511206e068c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Mon Mar 28 20:51:41 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207028, encodeId=a940120e02876, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Tue Mar 29 21:42:39 CST 2022, time=2022-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207684, encodeId=3236120e684fe, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Thu Mar 31 22:16:25 CST 2022, time=2022-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557276, encodeId=fae6155e27678, content=<a href='/topic/show?id=d5e281610db' target=_blank style='color:#2F92EE;'>#肠系膜#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81610, encryptionId=d5e281610db, topicName=肠系膜)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f84f14890130, createdName=zzc2216, createdTime=Mon Mar 21 09:46:03 CST 2022, time=2022-03-21, status=1, ipAttribution=)]
    2022-03-31 杨海东

    学习

    1

    展开1条回复
  7. [GetPortalCommentsPageByObjectIdResponse(id=1978002, encodeId=f85919e800240, content=<a href='/topic/show?id=20411e958de' target=_blank style='color:#2F92EE;'>#TVB#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17958, encryptionId=20411e958de, topicName=TVB)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1a5a149, createdName=gongliu, createdTime=Wed Dec 21 11:46:03 CST 2022, time=2022-12-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925578, encodeId=5bce19255e84b, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Aug 24 20:46:03 CST 2022, time=2022-08-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1206678, encodeId=bc0c12066e84b, content=好文章,值得一读。, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Mon Mar 28 19:04:54 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1206706, encodeId=5c511206e068c, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Mon Mar 28 20:51:41 CST 2022, time=2022-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207028, encodeId=a940120e02876, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Tue Mar 29 21:42:39 CST 2022, time=2022-03-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1207684, encodeId=3236120e684fe, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Thu Mar 31 22:16:25 CST 2022, time=2022-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1557276, encodeId=fae6155e27678, content=<a href='/topic/show?id=d5e281610db' target=_blank style='color:#2F92EE;'>#肠系膜#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81610, encryptionId=d5e281610db, topicName=肠系膜)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f84f14890130, createdName=zzc2216, createdTime=Mon Mar 21 09:46:03 CST 2022, time=2022-03-21, status=1, ipAttribution=)]
    2022-03-21 zzc2216

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