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JMCC：ROS保护心肌抵抗缺血再灌注损伤的新机制

2015-03-16 MedSci 上海生命科学研究院

ROS缺血再灌注心肌
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2月27日，Journal of Molecular and Cellular Cardiology （《分子与细胞心脏学期刊》）在线发表了中国科学院上海生命科学研究院健康科学研究所杨黄恬研究组题为ROS generated during early reperfusion contribute to intermittent hypobaric hypoxia-afforded cardiopr

2月27日，Journal of Molecular and Cellular Cardiology （《分子与细胞心脏学期刊》）在线发表了中国科学院上海生命科学研究院健康科学研究所杨黄恬研究组题为ROS generated during early reperfusion contribute to intermittent hypobaric hypoxia-afforded cardioprotection against postischemia-induced Ca2+ overload and contractile dysfunction via the JAK2/STAT3 pathway 的研究工作。该研究揭示了活性氧簇（ROS）在间歇性低压低氧（IHH）保护心脏抵抗心肌缺血再灌注损伤中的作用和新机制。


及时恢复血液灌注是临床上治疗缺血性心脏疾病的基本原则和手段，但该过程伴随着严重再灌注损伤的发生。缺血再灌注造成的钙离子超载和ROS大量释放是心肌细胞缺血再灌注损伤的主要原因。但ROS还可作为重要的信号分子参与细胞保护。健康所杨黄恬研究组新近发现心肌缺血后再灌注早期适量增高ROS具有抗心肌缺血再灌注损伤的保护作用，但其具体保护机制还有待解析。进一步理解ROS在缺血再灌注过程中所扮演的作用，深入解析其抵抗缺血再灌注的保护机制，对防治缺血性心脏病、发展心肌保护的新策略有着重要的意义。

吴兰、谭吉良等在研究人员杨黄恬的指导下，运用IHH作为心肌保护模型，探讨了ROS抵抗缺血再灌注损伤的保护机制。前期研究发现再灌注初期产生大量ROS，而在IHH保护模型中产生的ROS水平更高，研究人员由此提出假设，IHH的保护作用依赖于其复灌初期更高水平的ROS。在该研究中进一步发现复灌初期更高水平的ROS可通过有效激活JAK2/STAT3通路参与IHH的心肌保护作用；ROS激活的JAK2/STAT3通路通过抑制细胞内钙离子超载来实现心肌保护作用。进一步的机制研究表明，IHH通过ROS/JAK2/STAT3通路，促进Bcl-2在细胞内质网与内质网钙-ATP酶2（SERCA2）的相互作用，逆转缺血再灌注对SERCA2活性的抑制作用，进而维持了细胞内部的钙稳态，减轻缺血再灌注导致的心肌细胞钙离子超载、保护心肌。另一方面，复灌初期IHH升高ROS通过逆转缺血再灌注导致的线粒体STAT3磷酸化下降，改善缺血再灌注过程中线粒体内钙超载及其功能，从而保护心肌细胞，进而保护了整体心脏对抗缺血再灌注损伤。

该研究发现丰富了对ROS在心肌缺血再灌注损伤过程中所扮演的角色及其如何发挥作用的认识，并为开发基于ROS的缺血性心脏病的治疗措施提供了新的实验证据。

此研究得到了国家科技部和国家自然科学基金委项目的资助。

原始出处：
Wu L, Tan JL, Wang ZH, Chen YX, Gao L, Liu JL, Shi YH, Endoh M, Yang HT.ROS generated during early reperfusion contribute to intermittent hypobaric hypoxia-afforded cardioprotection against postischemia-induced Ca2+ overload and contractile dysfunction via the JAK2/STAT3 pathway. J Mol Cell Cardiol. 2015 Feb 27;81:150-161. doi: 10.1016/j.yjmcc.2015.02.015.

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1755706, encodeId=0f871e5570605, content=<a href='/topic/show?id=477a1031056' target=_blank style='color:#2F92EE;'>#JMCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10310, encryptionId=477a1031056, topicName=JMCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cae936999593, createdName=fyxzlh, createdTime=Thu Nov 05 18:55:00 CST 2015, time=2015-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1763573, encodeId=5b041e63573f3, content=<a href='/topic/show?id=8c323064e09' target=_blank style='color:#2F92EE;'>#再灌注损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30647, encryptionId=8c323064e09, topicName=再灌注损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56da37541085, createdName=ms9833124466084992, createdTime=Mon Dec 14 16:55:00 CST 2015, time=2015-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364017, encodeId=9c16136401e1a, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1396911, encodeId=6446139691175, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=18417, encodeId=bb151841e20, content=ROS双面性, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Tue Mar 17 07:23:00 CST 2015, time=2015-03-17, status=1, ipAttribution=)]
    2015-11-05 fyxzlh

    #JMCC#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1755706, encodeId=0f871e5570605, content=<a href='/topic/show?id=477a1031056' target=_blank style='color:#2F92EE;'>#JMCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10310, encryptionId=477a1031056, topicName=JMCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cae936999593, createdName=fyxzlh, createdTime=Thu Nov 05 18:55:00 CST 2015, time=2015-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1763573, encodeId=5b041e63573f3, content=<a href='/topic/show?id=8c323064e09' target=_blank style='color:#2F92EE;'>#再灌注损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30647, encryptionId=8c323064e09, topicName=再灌注损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56da37541085, createdName=ms9833124466084992, createdTime=Mon Dec 14 16:55:00 CST 2015, time=2015-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364017, encodeId=9c16136401e1a, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1396911, encodeId=6446139691175, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=18417, encodeId=bb151841e20, content=ROS双面性, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Tue Mar 17 07:23:00 CST 2015, time=2015-03-17, status=1, ipAttribution=)]
    2015-12-14 ms9833124466084992

    #再灌注损伤#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1755706, encodeId=0f871e5570605, content=<a href='/topic/show?id=477a1031056' target=_blank style='color:#2F92EE;'>#JMCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10310, encryptionId=477a1031056, topicName=JMCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cae936999593, createdName=fyxzlh, createdTime=Thu Nov 05 18:55:00 CST 2015, time=2015-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1763573, encodeId=5b041e63573f3, content=<a href='/topic/show?id=8c323064e09' target=_blank style='color:#2F92EE;'>#再灌注损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30647, encryptionId=8c323064e09, topicName=再灌注损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56da37541085, createdName=ms9833124466084992, createdTime=Mon Dec 14 16:55:00 CST 2015, time=2015-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364017, encodeId=9c16136401e1a, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1396911, encodeId=6446139691175, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=18417, encodeId=bb151841e20, content=ROS双面性, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Tue Mar 17 07:23:00 CST 2015, time=2015-03-17, status=1, ipAttribution=)]
    2015-03-18 lsndxfj

    #ROS#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1755706, encodeId=0f871e5570605, content=<a href='/topic/show?id=477a1031056' target=_blank style='color:#2F92EE;'>#JMCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10310, encryptionId=477a1031056, topicName=JMCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cae936999593, createdName=fyxzlh, createdTime=Thu Nov 05 18:55:00 CST 2015, time=2015-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1763573, encodeId=5b041e63573f3, content=<a href='/topic/show?id=8c323064e09' target=_blank style='color:#2F92EE;'>#再灌注损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30647, encryptionId=8c323064e09, topicName=再灌注损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56da37541085, createdName=ms9833124466084992, createdTime=Mon Dec 14 16:55:00 CST 2015, time=2015-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364017, encodeId=9c16136401e1a, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1396911, encodeId=6446139691175, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=18417, encodeId=bb151841e20, content=ROS双面性, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Tue Mar 17 07:23:00 CST 2015, time=2015-03-17, status=1, ipAttribution=)]
    2015-03-18 智者为医08

    #损伤#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1755706, encodeId=0f871e5570605, content=<a href='/topic/show?id=477a1031056' target=_blank style='color:#2F92EE;'>#JMCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10310, encryptionId=477a1031056, topicName=JMCC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cae936999593, createdName=fyxzlh, createdTime=Thu Nov 05 18:55:00 CST 2015, time=2015-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1763573, encodeId=5b041e63573f3, content=<a href='/topic/show?id=8c323064e09' target=_blank style='color:#2F92EE;'>#再灌注损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30647, encryptionId=8c323064e09, topicName=再灌注损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56da37541085, createdName=ms9833124466084992, createdTime=Mon Dec 14 16:55:00 CST 2015, time=2015-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1364017, encodeId=9c16136401e1a, content=<a href='/topic/show?id=7c5615628ad' target=_blank style='color:#2F92EE;'>#ROS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15628, encryptionId=7c5615628ad, topicName=ROS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1396911, encodeId=6446139691175, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Mar 18 11:55:00 CST 2015, time=2015-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=18417, encodeId=bb151841e20, content=ROS双面性, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Tue Mar 17 07:23:00 CST 2015, time=2015-03-17, status=1, ipAttribution=)]
    2015-03-17 medcardio

    ROS双面性

    0

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