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Article(id=1203036771912217047, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203036770628755576, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2022.04.0456, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1649952000000, receivedDateStr=2022-04-15, revisedDate=null, revisedDateStr=null, acceptedDate=1656345600000, acceptedDateStr=2022-06-28, onlineDate=1764755917766, onlineDateStr=2025-12-03, pubDate=1682611200000, pubDateStr=2023-04-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764755917766, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764755917766, creator=13701087609, updateTime=1764755917766, updator=13701087609, issue=Issue{id=1203036770628755576, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='4', pageStart='367', pageEnd='488', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764755917460, creator=13701087609, updateTime=1764756108290, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203037571086508742, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203036770628755576, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203037571086508743, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203036770628755576, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=456, endPage=460, ext={EN=ArticleExt(id=1203036772172263897, articleId=1203036771912217047, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Research progress on the role of adaptor protein p66Shc in myocardial ischemia-reperfusion injury, columnId=1190243275882729994, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Ischemic heart disease (IHD) is one of the diseases with the highest mortality in the world, which endangers human health for a long term. Reperfusion, the preferred treatment strategy, can lead to myocardial deterioration and accelerate injury, known as myocardial ischemia-reperfusion injury (MIRI), which seriously affects the clinical efficacy and prognosis of patients. At present, the prevention and treatment of MIRI is still an unsolved clinical problem. Numerous studies have shown that adaptor protein p66Shc plays an important regulatory role in the occurrence and development of various diseases, including MIRI.The mechanism of adaptor protein p66Shc involved in oxidative stress, inflammatory response and vascular endothelial function in MIRI, and the relevant treatment strategies targeting p66Shc were reviewed in present paper in order to provide a reference for further research on prevention and treatment of MIRI.

, correspAuthors=Zheng Zhang, authorNote=null, correspAuthorsNote=
E-mail:
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缺血性心脏病是全世界死亡率较高的疾病之一，长期危害着人类的健康，其首选治疗策略再灌注可导致心肌缺血恶化及加速损伤，即心肌缺血再灌注损伤（MIRI），严重影响临床疗效及患者预后。目前MIRI的预防和治疗仍是临床尚未解决的难题。大量研究表明，衔接蛋白p66Shc在包括MIRI对内的多种疾病的发生发展具有重要的调控作用。本文针对衔接蛋白p66Shc在MIRI氧化应激、炎症反应和血管内皮功能障碍中的调节作用机制，以及以p66Shc为靶点的相关治疗策略进行综述，以期为MIRI的预防和治疗提供进一步的参考。

, correspAuthors=张钲, authorNote=null, correspAuthorsNote=
张钲，E-mail：
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王沛，硕士研究生，主要从事心血管疾病方面的研究

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王沛，硕士研究生，主要从事心血管疾病方面的研究

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王沛，硕士研究生，主要从事心血管疾病方面的研究

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Global health observatory data repository[J]. Med Ref Serv Q, 2020, 39(1): 67-74., articleTitle=Global health observatory data repository, refAbstract=null), Reference(id=1203036775850668646, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=29, issue=2, pageStart=420, pageEnd=431, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=Safiri S, Karamzad N, Singh K, journalName=Eur J Prev Cardiol, refType=null, unstructuredReference=Safiri S, Karamzad N, Singh K, et al. Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990-2019[J]. Eur J Prev Cardiol, 2022, 29(2): 420-431., articleTitle=Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990-2019, refAbstract=null), Reference(id=1203036775938749039, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2020, volume=45, issue=11, pageStart=1161, pageEnd=1166, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=Han LM, Luo XH, Zhao HL, journalName=Med J Chin PLA, refType=null, unstructuredReference=Han LM, Luo XH, Zhao HL. Research progress on mechanism of autophagy regulatory factor mTOR in myocardial ischemia-reperfusion injury[J]. Med J Chin PLA, 2020, 45(11): 1161-1166., articleTitle=Research progress on mechanism of autophagy regulatory factor mTOR in myocardial ischemia-reperfusion injury, refAbstract=null), Reference(id=1203036776026829428, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2020, volume=45, issue=11, pageStart=1161, pageEnd=1166, url=null, language=null, rfNumber=[3], rfOrder=3, authorNames=韩利民, 罗小红, 赵海龙, journalName=解放军医学杂志, refType=null, unstructuredReference=[韩利民, 罗小红, 赵海龙. 自噬调控因子mTOR对心肌缺血再灌注损伤的作用机制研究进展[J]. 解放军医学杂志, 2020, 45(11): 1161-1166.], articleTitle=自噬调控因子mTOR对心肌缺血再灌注损伤的作用机制研究进展, refAbstract=null), Reference(id=1203036776131687033, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2021, volume=27, issue=3, pageStart=248, pageEnd=262, url=null, language=null, rfNumber=[4], rfOrder=4, authorNames=Martins-Marques T, Hausenloy DJ, Sluijter JPG, journalName=Trends Mol Med, refType=null, unstructuredReference=Martins-Marques T, Hausenloy DJ, Sluijter JPG, et al.Intercellular communication in the heart: therapeutic opportunities for cardiac ischemia[J]. Trends Mol Med, 2021, 27(3): 248-262., articleTitle=Intercellular communication in the heart: therapeutic opportunities for cardiac ischemia, refAbstract=null), Reference(id=1203036776236544643, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=23, issue=6, pageStart=430, pageEnd=null, url=null, language=null, rfNumber=[5], rfOrder=5, authorNames=He J, Liu D, Zhao L, journalName=Exp Ther Med, refType=null, unstructuredReference=He J, Liu D, Zhao L, et al. Myocardial ischemia/reperfusion injury: mechanisms of injury and implications for management(Review)[J]. Exp Ther Med, 2022, 23(6): 430., articleTitle=Myocardial ischemia/reperfusion injury: mechanisms of injury and implications for management(Review), refAbstract=null), Reference(id=1203036776328819342, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=92, issue=null, pageStart=110266, pageEnd=null, url=null, language=null, rfNumber=[6], rfOrder=6, authorNames=Jia L, Yang L, Tian Y, journalName=Cell Signal, refType=null, unstructuredReference=Jia L, Yang L, Tian Y, et al. Nrf2 participates in the protective effect of exogenous mitochondria against mitochondrial dysfunction in myocardial ischaemic and hypoxic injury[J]. Cell Signal, 2022, 92: 110266., articleTitle=Nrf2 participates in the protective effect of exogenous mitochondria against mitochondrial dysfunction in myocardial ischaemic and hypoxic injury, refAbstract=null), Reference(id=1203036776412705429, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2017, volume=8, issue=null, pageStart=733, pageEnd=null, url=null, language=null, rfNumber=[7], rfOrder=7, authorNames=Boengler K, Bencsik P, Palóczi J, journalName=Front Physiol, refType=null, unstructuredReference=Boengler K, Bencsik P, Palóczi J, et al. Lack of contribution of p66shc and its mitochondrial translocation to ischemia-reperfusion injury and cardioprotection by ischemic preconditioning[J]. Front Physiol, 2017, 8: 733., articleTitle=Lack of contribution of p66shc and its mitochondrial translocation to ischemia-reperfusion injury and cardioprotection by ischemic preconditioning, refAbstract=null), Reference(id=1203036776538534560, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2018, volume=314, issue=2, pageStart=F143, pageEnd=F153, url=null, language=null, rfNumber=[8], rfOrder=8, authorNames=Wright KD, Staruschenko A, Sorokin A, journalName=Am J Physiol Renal Physiol, refType=null, unstructuredReference=Wright KD, Staruschenko A, Sorokin A. Role of adaptor protein p66Shc in renal pathologies[J]. Am J Physiol Renal Physiol, 2018, 314(2): F143-F153., articleTitle=Role of adaptor protein p66Shc in renal pathologies, refAbstract=null), Reference(id=1203036776635003557, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2020, volume=63, issue=null, pageStart=101139, pageEnd=null, url=null, language=null, rfNumber=[9], rfOrder=9, authorNames=Mir HA, Ali R, Mushtaq U, journalName=Ageing Res Rev, refType=null, unstructuredReference=Mir HA, Ali R, Mushtaq U, et al. Structure-functional implications of longevity protein p66Shc in health and disease[J]. Ageing Res Rev, 2020, 63: 101139., articleTitle=Structure-functional implications of longevity protein p66Shc in health and disease, refAbstract=null), Reference(id=1203036776765026989, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2021, volume=46, issue=5, pageStart=512, pageEnd=517, url=null, language=null, rfNumber=[10], rfOrder=10, authorNames=Chen C, Liu H, Lin YG, journalName=Med J Chin PLA, refType=null, unstructuredReference=Chen C, Liu H, Lin YG, et al. Research progress on the role of sarcopenia in the pathogenesis of atherosclerotic cardio-cerebrovascular disease in the elderly[J]. Med J Chin PLA, 2021, 46(5): 512-517., articleTitle=Research progress on the role of sarcopenia in the pathogenesis of atherosclerotic cardio-cerebrovascular disease in the elderly, refAbstract=null), Reference(id=1203036776878273206, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2021, volume=46, issue=5, pageStart=512, pageEnd=517, url=null, language=null, rfNumber=[10], rfOrder=11, authorNames=陈长, 刘辉, 蔺阳刚, journalName=解放军医学杂志, refType=null, unstructuredReference=[陈长, 刘辉, 蔺阳刚, 等. 肌少症在老年动脉粥样硬化性心血管疾病发病中的作用研究进展[J]. 解放军医学杂志, 2021, 46(5): 512-517.], articleTitle=肌少症在老年动脉粥样硬化性心血管疾病发病中的作用研究进展, refAbstract=null), Reference(id=1203036776953770686, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=11, issue=3, pageStart=552, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=12, authorNames=Hajam YA, Rani R, Ganie SY, journalName=Cells, refType=null, unstructuredReference=Hajam YA, Rani R, Ganie SY, et al. Oxidative stress in human pathology and aging: molecular mechanisms and perspectives[J].Cells, 2022, 11(3): 552., articleTitle=Oxidative stress in human pathology and aging: molecular mechanisms and perspectives, refAbstract=null), Reference(id=1203036777046045380, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=10, issue=1, pageStart=127, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=13, authorNames=Adameova A, Horvath C, Abdul-Ghani S, journalName=Biomedicines, refType=null, unstructuredReference=Adameova A, Horvath C, Abdul-Ghani S, et al. Interplay of oxidative stress and necrosis-like cell death in cardiac ischemia/reperfusion injury: a focus on necroptosis[J]. Biomedicines, 2022, 10(1): 127., articleTitle=Interplay of oxidative stress and necrosis-like cell death in cardiac ischemia/reperfusion injury: a focus on necroptosis, refAbstract=null), Reference(id=1203036777142514378, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2019, volume=114, issue=4, pageStart=29, pageEnd=null, url=null, language=null, rfNumber=[13], rfOrder=14, authorNames=Boengler K, Bornbaum J, Schlüter KD, journalName=Basic Res Cardiol, refType=null, unstructuredReference=Boengler K, Bornbaum J, Schlüter KD, et al. P66shc and its role in ischemic cardiovascular diseases[J]. Basic Res Cardiol, 2019, 114(4): 29., articleTitle=P66shc and its role in ischemic cardiovascular diseases, refAbstract=null), Reference(id=1203036777222206162, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2004, volume=24, issue=4, pageStart=1747, pageEnd=1757, url=null, language=null, rfNumber=[14], rfOrder=15, authorNames=Pacini S, Pellegrini M, Migliaccio E, journalName=Mol Cell Biol, refType=null, unstructuredReference=Pacini S, Pellegrini M, Migliaccio E, et al. p66SHC promotes apoptosis and antagonizes mitogenic signaling in T cells[J]. Mol Cell Biol, 2004, 24(4): 1747-1757., articleTitle=p66SHC promotes apoptosis and antagonizes mitogenic signaling in T cells, refAbstract=null), Reference(id=1203036777335452383, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=1999, volume=402, issue=6759, pageStart=309, pageEnd=313, url=null, language=null, rfNumber=[15], rfOrder=16, authorNames=Migliaccio E, Giorgio M, Mele S, journalName=Nature, refType=null, unstructuredReference=Migliaccio E, Giorgio M, Mele S, et al. The p66shc adaptor protein controls oxidative stress response and life span in mammals[J]. Nature, 1999, 402(6759): 309-313., articleTitle=The p66shc adaptor protein controls oxidative stress response and life span in mammals, refAbstract=null), Reference(id=1203036777423532775, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2021, volume=6, issue=8, pageStart=631, pageEnd=646, url=null, language=null, rfNumber=[16], rfOrder=17, authorNames=Veltman D, Wu M, Pokreisz P, journalName=JACC Basic Transl Sci, refType=null, unstructuredReference=Veltman D, Wu M, Pokreisz P, et al. Clec4e-receptor signaling in myocardial repair after ischemia-reperfusion injury[J]. JACC Basic Transl Sci, 2021, 6(8): 631-646., articleTitle=Clec4e-receptor signaling in myocardial repair after ischemia-reperfusion injury, refAbstract=null), Reference(id=1203036777499030254, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2021, volume=23, issue=5, pageStart=374, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=18, authorNames=Yang YY, Deng RR, Chen Z, journalName=Mol Med Rep, refType=null, unstructuredReference=Yang YY, Deng RR, Chen Z, et al. Piperazine ferulate attenuates high glucose-induced mesangial cell injury via the regulation of p66Shc[J]. Mol Med Rep, 2021, 23(5): 374., articleTitle=Piperazine ferulate attenuates high glucose-induced mesangial cell injury via the regulation of p66Shc, refAbstract=null), Reference(id=1203036777574527731, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2016, volume=164, issue=null, pageStart=1, pageEnd=8, url=null, language=null, rfNumber=[18], rfOrder=19, authorNames=Zhang M, Xie Y, Yan R, journalName=Life Sci, refType=null, unstructuredReference=Zhang M, Xie Y, Yan R, et al. Curcumin ameliorates alveolar epithelial injury in a rat model of chronic obstructive pulmonary disease[J]. Life Sci, 2016, 164: 1-8., articleTitle=Curcumin ameliorates alveolar epithelial injury in a rat model of chronic obstructive pulmonary disease, refAbstract=null), Reference(id=1203036777654219514, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=20, authorNames=Algoet M, Janssens S, Himmelreich U, journalName=Trends Cardiovasc Med, refType=null, unstructuredReference=Algoet M, Janssens S, Himmelreich U, et al. Myocardial ischemia-reperfusion injury and the influence of inflammation[J]. Trends Cardiovasc Med, 2022. doi: 10.1016/j.tcm.2022.02.005., articleTitle=Myocardial ischemia-reperfusion injury and the influence of inflammation, refAbstract=null), Reference(id=1203036777717134082, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2019, volume=9, issue=5, pageStart=1510, pageEnd=1522, url=null, language=null, rfNumber=[20], rfOrder=21, authorNames=Zhao Y, Wang Z, Feng D, journalName=Theranostics, refType=null, unstructuredReference=Zhao Y, Wang Z, Feng D, et al. p66Shc contributes to liver fibrosis through the regulation of mitochondrial reactive oxygen species[J]. Theranostics, 2019, 9(5): 1510-1522., articleTitle=p66Shc contributes to liver fibrosis through the regulation of mitochondrial reactive oxygen species, refAbstract=null), Reference(id=1203036777809408778, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=55, issue=1, pageStart=30, pageEnd=38, url=null, language=null, rfNumber=[21], rfOrder=22, authorNames=Kang IS, Kwon K, journalName=BMB Rep, refType=null, unstructuredReference=Kang IS, Kwon K. Potential application of biomimetic exosomes in cardiovascular disease: focused on ischemic heart disease[J].BMB Rep, 2022, 55(1): 30-38., articleTitle=Potential application of biomimetic exosomes in cardiovascular disease: focused on ischemic heart disease, refAbstract=null), Reference(id=1203036777884906253, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=23, issue=1, pageStart=23, pageEnd=null, url=null, language=null, rfNumber=[22], rfOrder=23, authorNames=He JZ, Bellenger NG, Ludman AJ, journalName=Rev Cardiovasc Med, refType=null, unstructuredReference=He JZ, Bellenger NG, Ludman AJ, et al. Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: promise, disappointment, and hope[J]. Rev Cardiovasc Med, 2022, 23(1): 23., articleTitle=Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: promise, disappointment, and hope, refAbstract=null), Reference(id=1203036777956209429, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2021, volume=12, issue=null, pageStart=787541, pageEnd=null, url=null, language=null, rfNumber=[23], rfOrder=24, authorNames=Botts SR, Fish JE, Howe KL, journalName=Front Pharmacol, refType=null, unstructuredReference=Botts SR, Fish JE, Howe KL. Dysfunctional vascular endothelium as a driver of atherosclerosis: emerging insights into pathogenesis and treatment[J]. Front Pharmacol, 2021, 12: 787541., articleTitle=Dysfunctional vascular endothelium as a driver of atherosclerosis: emerging insights into pathogenesis and treatment, refAbstract=null), Reference(id=1203036778056872732, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2021, volume=223, issue=null, pageStart=107819, pageEnd=null, url=null, language=null, rfNumber=[24], rfOrder=25, authorNames=Griffiths K, Lee JJ, Frenneaux MP, journalName=Pharmacol Ther, refType=null, unstructuredReference=Griffiths K, Lee JJ, Frenneaux MP, et al. Nitrite and myocardial ischaemia reperfusion injury. Where are we now?[J]. Pharmacol Ther, 2021, 223: 107819., articleTitle=Nitrite and myocardial ischaemia reperfusion injury. Where are we now?, refAbstract=null), Reference(id=1203036778136564513, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2004, volume=110, issue=18, pageStart=2889, pageEnd=2895, url=null, language=null, rfNumber=[25], rfOrder=26, authorNames=Francia P, delli Gatti C, Bachschmid M, journalName=Circulation, refType=null, unstructuredReference=Francia P, delli Gatti C, Bachschmid M, et al. Deletion of p66shc gene protects against age-related endothelial dysfunction[J].Circulation, 2004, 110(18): 2889-2895., articleTitle=Deletion of p66shc gene protects against age-related endothelial dysfunction, refAbstract=null), Reference(id=1203036778216256296, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2014, volume=175, issue=3, pageStart=446, pageEnd=450, url=null, language=null, rfNumber=[26], rfOrder=27, authorNames=Shi Y, Savarese G, Perrone-Filardi P, journalName=Int J Cardiol, refType=null, unstructuredReference=Shi Y, Savarese G, Perrone-Filardi P, et al. Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc[J]. Int J Cardiol, 2014, 175(3): 446-450., articleTitle=Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc, refAbstract=null), Reference(id=1203036778333696821, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2005, volume=39, issue=6, pageStart=992, pageEnd=995, url=null, language=null, rfNumber=[27], rfOrder=28, authorNames=Yamamori T, White AR, Mattagajasingh I, journalName=J Mol Cell Cardiol, refType=null, unstructuredReference=Yamamori T, White AR, Mattagajasingh I, et al. P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction[J]. J Mol Cell Cardiol, 2005, 39(6): 992-995., articleTitle=P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction, refAbstract=null), Reference(id=1203036778451137334, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2014, volume=64, issue=2, pageStart=347, pageEnd=353, url=null, language=null, rfNumber=[28], rfOrder=29, authorNames=Spescha RD, Glanzmann M, Simic B, journalName=Hypertension, refType=null, unstructuredReference=Spescha RD, Glanzmann M, Simic B, et al. Adaptor protein p66(Shc) mediates hypertension-associated, cyclic stretch-dependent, endothelial damage[J]. Hypertension, 2014, 64(2): 347-353., articleTitle=Adaptor protein p66(Shc) mediates hypertension-associated, cyclic stretch-dependent, endothelial damage, refAbstract=null), Reference(id=1203036778602132285, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2019, volume=139, issue=19, pageStart=2260, pageEnd=2277, url=null, language=null, rfNumber=[29], rfOrder=30, authorNames=Xiao Y, Xia J, Cheng J, journalName=Circulation, refType=null, unstructuredReference=Xiao Y, Xia J, Cheng J, et al. Inhibition of S-adenosylhomo-cysteine hydrolase induces endothelial dysfunction via epigenetic regulation of p66shc-mediated oxidative stress pathway[J].Circulation, 2019, 139(19): 2260-2277., articleTitle=Inhibition of S-adenosylhomo-cysteine hydrolase induces endothelial dysfunction via epigenetic regulation of p66shc-mediated oxidative stress pathway, refAbstract=null), Reference(id=1203036778711184197, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2016, volume=126, issue=7, pageStart=2533, pageEnd=2546, url=null, language=null, rfNumber=[30], rfOrder=31, authorNames=Miller B, Palygin O, Rufanova VA, journalName=J Clin Invest, refType=null, unstructuredReference=Miller B, Palygin O, Rufanova VA, et al. p66Shc regulates renal vascular tone in hypertension-induced nephropathy[J]. J Clin Invest, 2016, 126(7): 2533-2546., articleTitle=p66Shc regulates renal vascular tone in hypertension-induced nephropathy, refAbstract=null), Reference(id=1203036778820236110, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2012, volume=303, issue=2, pageStart=H189, pageEnd=H196, url=null, language=null, rfNumber=[31], rfOrder=32, authorNames=Kim YR, Kim CS, Naqvi A, journalName=Am J Physiol Heart Circ Physiol, refType=null, unstructuredReference=Kim YR, Kim CS, Naqvi A, et al. Epigenetic upregulation of p66shc mediates low-density lipoprotein cholesterol-induced endothelial cell dysfunction[J]. Am J Physiol Heart Circ Physiol, 2012, 303(2): H189-H196., articleTitle=Epigenetic upregulation of p66shc mediates low-density lipoprotein cholesterol-induced endothelial cell dysfunction, refAbstract=null), Reference(id=1203036778904122199, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2019, volume=39, issue=4, pageStart=BSR20182134, pageEnd=null, url=null, language=null, rfNumber=[32], rfOrder=33, authorNames=Kumar S, journalName=Biosci Rep, refType=null, unstructuredReference=Kumar S. P66Shc and vascular endothelial function[J]. Biosci Rep, 2019, 39(4): BSR20182134., articleTitle=P66Shc and vascular endothelial function, refAbstract=null), Reference(id=1203036779008979808, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2000, volume=14, issue=9, pageStart=1132, pageEnd=1145, url=null, language=null, rfNumber=[33], rfOrder=34, authorNames=Lai KM, Pawson T, journalName=Genes Dev, refType=null, unstructuredReference=Lai KM, Pawson T. The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo[J].Genes Dev, 2000, 14(9): 1132-1145., articleTitle=The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo, refAbstract=null), Reference(id=1203036779080282982, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2014, volume=111, issue=4, pageStart=610, pageEnd=617, url=null, language=null, rfNumber=[34], rfOrder=35, authorNames=Bock F, Shahzad K, Vergnolle N, journalName=Thromb Haemost, refType=null, unstructuredReference=Bock F, Shahzad K, Vergnolle N, et al. Activated protein C based therapeutic strategies in chronic diseases[J]. Thromb Haemost, 2014, 111(4): 610-617., articleTitle=Activated protein C based therapeutic strategies in chronic diseases, refAbstract=null), Reference(id=1203036779155780461, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2017, volume=114, issue=7, pageStart=1714, pageEnd=1719, url=null, language=null, rfNumber=[35], rfOrder=36, authorNames=Kumar S, Kim YR, Vikram A, journalName=Proc Natl Acad Sci U S A, refType=null, unstructuredReference=Kumar S, Kim YR, Vikram A, et al. Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction[J]. Proc Natl Acad Sci U S A, 2017, 114(7): 1714-1719., articleTitle=Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction, refAbstract=null), Reference(id=1203036779243860850, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2017, volume=131, issue=8, pageStart=759, pageEnd=773, url=null, language=null, rfNumber=[36], rfOrder=37, authorNames=Feng D, Yao J, Wang G, journalName=Clin Sci (Lond), refType=null, unstructuredReference=Feng D, Yao J, Wang G, et al. Inhibition of p66Shc-mediated mitochondrial apoptosis via targeting prolyl-isomerase Pin1 attenuates intestinal ischemia/reperfusion injury in rats[J]. Clin Sci (Lond), 2017, 131(8): 759-773., articleTitle=Inhibition of p66Shc-mediated mitochondrial apoptosis via targeting prolyl-isomerase Pin1 attenuates intestinal ischemia/reperfusion injury in rats, refAbstract=null), Reference(id=1203036779352912760, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=22, issue=3, pageStart=410, pageEnd=421, url=null, language=null, rfNumber=[37], rfOrder=38, authorNames=Zaib S, Saleem MA, Khan I, journalName=Mini Rev Med Chem, refType=null, unstructuredReference=Zaib S, Saleem MA, Khan I. CRISPR-Cas9 genome engineering: trends in medicine and health[J]. Mini Rev Med Chem, 2022, 22(3): 410-421., articleTitle=CRISPR-Cas9 genome engineering: trends in medicine and health, refAbstract=null), Reference(id=1203036779432604544, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036771912217047, doi=null, pmid=null, pmcid=null, year=2022, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[38], rfOrder=39, authorNames=Samaja M, Pagliaro P, journalName=Trends Cardiovasc Med, refType=null, unstructuredReference=Samaja M, Pagliaro P. Long and narrow road to win over myocardial ischemia-reperfusion injury[J]. 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衔接蛋白p66Shc在心肌缺血再灌注损伤中的作用研究进展
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王沛 1 , 剡冬冬 2, 3 , 彭瑜 2, 3 , 张钲 1, 2, 3, *
解放军医学杂志 | 综述 2023,48(4): 456-460
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解放军医学杂志 | 综述 2023, 48(4): 456-460
衔接蛋白p66Shc在心肌缺血再灌注损伤中的作用研究进展
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王沛1, 剡冬冬2, 3, 彭瑜2, 3, 张钲1, 2, 3, *
作者信息
  • 1兰州大学第一临床医学院，甘肃兰州 730000
  • 2兰州大学第一医院心脏中心，甘肃兰州 730000
  • 3甘肃省心血管病重点实验室，甘肃兰州 730000

    • 王沛，硕士研究生，主要从事心血管疾病方面的研究

通讯作者:

张钲，E-mail：
Research progress on the role of adaptor protein p66Shc in myocardial ischemia-reperfusion injury
Pei Wang1, Dong-Dong Yan2, 3, Yu Peng2, 3, Zheng Zhang1, 2, 3, *
Affiliations
  • 1The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, China
  • 2Department of Cardiology, the First Hospital of Lanzhou University, Lanzhou, Gansu 730000, China
  • 3Gansu Key Laboratory of Cardiovascular Disease, Lanzhou, Gansu 730000, China
出版时间: 2023-04-28 doi: 10.11855/j.issn.0577-7402.2022.04.0456
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摘要
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缺血性心脏病是全世界死亡率较高的疾病之一，长期危害着人类的健康，其首选治疗策略再灌注可导致心肌缺血恶化及加速损伤，即心肌缺血再灌注损伤（MIRI），严重影响临床疗效及患者预后。目前MIRI的预防和治疗仍是临床尚未解决的难题。大量研究表明，衔接蛋白p66Shc在包括MIRI对内的多种疾病的发生发展具有重要的调控作用。本文针对衔接蛋白p66Shc在MIRI氧化应激、炎症反应和血管内皮功能障碍中的调节作用机制，以及以p66Shc为靶点的相关治疗策略进行综述，以期为MIRI的预防和治疗提供进一步的参考。

缺血性心脏病  /  心肌缺血再灌注损伤  /  p66Shc  /  氧化应激

Ischemic heart disease (IHD) is one of the diseases with the highest mortality in the world, which endangers human health for a long term. Reperfusion, the preferred treatment strategy, can lead to myocardial deterioration and accelerate injury, known as myocardial ischemia-reperfusion injury (MIRI), which seriously affects the clinical efficacy and prognosis of patients. At present, the prevention and treatment of MIRI is still an unsolved clinical problem. Numerous studies have shown that adaptor protein p66Shc plays an important regulatory role in the occurrence and development of various diseases, including MIRI.The mechanism of adaptor protein p66Shc involved in oxidative stress, inflammatory response and vascular endothelial function in MIRI, and the relevant treatment strategies targeting p66Shc were reviewed in present paper in order to provide a reference for further research on prevention and treatment of MIRI.

ischemic heart disease  /  myocardial ischaemia-reperfusion injury  /  p66Shc  /  oxidative stress
王沛, 剡冬冬, 彭瑜, 张钲. 衔接蛋白p66Shc在心肌缺血再灌注损伤中的作用研究进展. 解放军医学杂志, 2023 , 48 (4) : 456 -460 . DOI: 10.11855/j.issn.0577-7402.2022.04.0456
Pei Wang, Dong-Dong Yan, Yu Peng, Zheng Zhang. Research progress on the role of adaptor protein p66Shc in myocardial ischemia-reperfusion injury[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (4) : 456 -460 . DOI: 10.11855/j.issn.0577-7402.2022.04.0456
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缺血性心脏病（ischemic heart disease，IHD）是全球致死率较高的疾病之一[1]。一项调查显示，2019年全球IHD患病人数1.972亿，因IHD死亡的人数为910万[2]。随着早期血运重建技术的发展，IHD病死率有所下降，但心肌血流再灌注导致的继发性心肌损伤严重影响IHD患者的预后。心肌缺血再灌注损伤（myocardial ischaemia-reperfusion injury，MIRI）是指缺血心肌在血流恢复后缺血损伤加重的病理现象[3]，极大地降低了心血管疾病的治疗效果[4]。MIRI包括4种损伤类型：（1）以心肌细胞死亡增多为特征的致死性再灌注损伤；（2）以微血管床进行性损伤、无血流区扩大及冠状动脉储备功能丧失为特征的再灌注性血管损伤；（3）心肌细胞代谢受损和收缩功能异常导致的心肌顿抑；（4）以室性心动过速为主的再灌注性心律失常。MIRI的病理生理机制复杂，迄今为止尚未完全阐明[5]。心肌缺血缺氧及再灌注可导致氧化磷酸化障碍，细胞色素C（Cyt C）、活性氧（ROS）的释放增多，促进线粒体通透性转换孔（mitochondrial permeability transition pore，mPTP）持续开放而使线粒体膜电位（ΔΨm）迅速丧失，同时还介导了包括氧化应激和炎症反应在内的一系列复杂机制，造成心肌进一步损伤，因此线粒体在MIRI发生发展中具有极其重要的作用[6]。近年来有研究发现，衔接蛋白p66Shc是线粒体功能障碍过程中的关键调节因子，受应激信号作用后在线粒体介导的MIRI中发挥重要作用，同时，p66Shc基因缺失或使用p66Shc磷酸化抑制剂也被证实对IHD发生MIRI具有保护效应[7]。因此，本文就p66Shc在MIRI中对氧化应激、炎症反应和血管内皮细胞功能障碍的调节机制以及靶向治疗策略的进展进行综述，以期为后续MIRI相关研究提供参考及思路。
1 p66Shc概述
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哺乳动物的SHC基因家族包括4个成员：ShcA、ShcB、ShcC和ShcD，其表达产物衔接蛋白通过介导细胞因子、生长因子和整合素诱导的各种细胞外信号参与调节人体的生理和病理过程。其中，ShcB、ShcC和ShcD基因主要在神经系统细胞中表达，并在神经发育中发挥作用，而ShcA基因在多种组织中表达[8]。ShcA基因位点定位于染色体1q21，包含13个外显子，编码分子量分别为46、52和66 ku的3种衔接蛋白p46Shc、p52Shc和p66Shc，3种亚型具有相似的核心结构域，包括高度保守的C端区域、N端磷酸酪氨酸结合区（PTB）、Src同源结构域（SH2），以及一个连接PTB结构域与SH2结构域的富含脯氨酸的同源结构域（CH1）。p66Shc与其他两种亚型的不同之处在于含有一个额外的片段连接到PTB结构域的N端，称为CH2结构域，使其成为该家族中最长的亚型。CH2结构域包含一个磷酸化丝氨酸残基36位点（Ser36）和Cyt C结构域，从而使p66Shc具有介导细胞增殖和凋亡的双重功能。在3种亚型中，p66Shc在除造血细胞系外的大多数细胞中表达，而p46Shc和p52Shc则在所有细胞中表达[9]。在生理条件下，大部分p66Shc存在于细胞质中，小部分存在于内质网及线粒体中；在应激信号的作用下，p66Shc的Ser36可被蛋白激酶C-β（PKC-β）磷酸化激活，再经过异构化及去磷酸化过程后通过内膜/外膜转运体转位至线粒体中，结合并氧化Cyt C，增加细胞内ROS水平，继而开放mPTP，导致线粒体功能障碍，最终促进细胞凋亡[7]。
2 p66Shc在心肌缺血再灌注损伤中的作用机制
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2.1 p66Shc与氧化应激
氧化应激在MIRI中的机制已被广泛报道[10]，而ROS正是介导氧化应激的关键信号分子。ROS主要来源于线粒体，尤其是在心肌细胞中，包括超氧阴离子（O2•）、羟基自由基（·OH）和H2O2等成分。生理条件下，细胞内氧化与抗氧化系统维持动态平衡，ROS作为信号分子调节细胞增殖、分化、代谢和凋亡等生理过程；而当细胞接受应激信号刺激，氧化与抗氧化之间的动态平衡遭到破坏后，则会产生大量以ROS为主的氧化剂，进而损伤DNA、蛋白质及脂质，导致细胞凋亡和坏死[11]。有研究发现，在心肌缺血过程中仅产生少量ROS，而ROS的大量产生则发生在心肌血流再灌注的过程中，过量的ROS会引起mPTP异常开放、钙超载、DNA损伤、蛋白质变性及脂质过氧化，从而导致线粒体功能障碍，并通过过度自噬和促炎反应共同诱导细胞凋亡甚至坏死，加剧心肌损伤[12]。
基于氧化应激在MIRI中的重要作用，如何通过抑制氧化应激来改善MIRI成为相关研究的重点。既往研究发现，p66Shc在MIRI的ROS生成中发挥重要作用[7]。具体来讲，p66Shc不仅可通过氧化Cyt C及抑制单分子氧还原来增加ROS的生成，还可通过抑制抗氧化酶的表达来减少ROS的代谢、增加细胞内的ROS水平；同时，ROS水平越高，p66Shc活化程度越高，细胞氧化应激损伤越重[13]。研究发现，促进p66Shc过表达可增强氧化应激对细胞的损伤，敲除小鼠p66Shc基因或转染p66Shc-/-质粒不但可减轻氧化应激对组织的损伤，而且可使小鼠寿命较对照组延长约30%[14-15]。可见，p66Shc是氧化应激中的关键信号分子，沉默或抑制p66Shc的表达可能成为预防及治疗MIRI的重要手段。
2.2 p66Shc与炎症反应
炎症是机体应对刺激时产生的防御反应，适度的炎症有利于机体维护内环境稳态，而过度的炎症则会对机体造成损害，引发一系列病理生理过程，最终导致疾病的发生发展。有研究发现，在心肌缺血再灌注过程中，虽然炎症在缺血期间已被诱导，但血流和氧气输送的恢复会进一步激活炎症信号通路，产生级联放大效应，其中白细胞介素（interleukin，IL）、中性粒细胞和炎性小体起着关键作用[16]。p66Shc除了通过调控氧化应激和ROS介导的多条促炎反应途径外，还对部分炎症介质、炎性细胞、促炎基因及炎性小体具有调控作用。Yang等[17]在针对糖尿病肾病的研究中发现，阿魏酸哌嗪可通过抑制p66Shc来降低血中IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）及细胞中ROS的水平，同时抑制促炎基因核转录因子-κB（nuclear factor-κB，NF-κB）的表达。另一项探索慢性阻塞性肺疾病的研究发现，姜黄素也可通过下调p66Shc的表达来降低疾病模型组大鼠血清中IL-6、IL-8和TNF-α的水平，并能减轻肺泡上皮细胞的凋亡[18]。此外，核苷酸结合寡聚化结构域样受体蛋白3（nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3，NLRP3）炎性小体作为许多促炎因子趋化的共同途径被广泛研究。IHD患者机体存在慢性炎症状态，MIRI过程中NLRP3炎性小体在机体慢性炎症与再灌注后的新发炎症中起着重要的桥接作用，其活化状态与MIRI的进展一致，可通过炎症级联放大效应促进心脏的不良重塑，同时加速心肌细胞的凋亡[19]。Zhao等[20]在研究p66Shc对肝纤维化的影响时发现，降低p66Shc的表达可明显抑制线粒体ROS的产生和NLRP3炎性小体的激活，而p66Shc过表达则产生相反的效果，提示抑制p66Shc的表达不但可调控氧化应激，还可减轻炎症反应，减少心肌细胞在MIRI过程中的损害，对改善IHD患者的心功能具有积极作用。
2.3 p66Shc与血管内皮细胞功能障碍
血管内皮受损是IHD发生发展的始动因素，两者相互促进，形成恶性循环[21]。近年来，研究者在探索MIRI发生发展机制的过程中发现，缺血缺氧与再灌注引起的氧化应激和炎症反应及二者介导的绝大多数病理过程均可损害冠状动脉内皮细胞的结构与功能，其中以冠状动脉微循环血管内皮为主，而冠状动脉微循环障碍可引起继发性的慢血流与无复流现象，进一步加重MIRI[22]。冠状动脉血管内皮细胞不但是血液与心肌细胞间的桥梁和屏障，而且可通过合成、释放包括收缩因子内皮素-1和舒张因子一氧化氮（nitric oxide，NO）在内的调节因子控制血管张力及管腔直径，从而维持血管稳态[23]。在心肌缺血再灌注过程中，内皮细胞NO释放量减少，使微血管张力增加，从而导致MIRI[24]。最初，研究者在对衰老小鼠的研究中发现，与野生型小鼠比较，p66Shc-/-小鼠由衰老引起的内皮功能障碍及ROS增加明显减轻[25]。后来的两项研究在p66Shc-/-衰老小鼠中同样发现p66Shc可通过调节血管内皮细胞的ROS和NO合成水平来影响内皮功能[26-27]。Spescha等[28]研究发现，血管张力增加可活化p66Shc，并降低血管内皮细胞的NO生物利用度，这可能会进一步增加血管张力并通过增强p66Shc介导的氧化应激和炎症反应来促进和加重MIRI。Xiao等[29]在研究S-腺苷同型半胱氨酸对动脉粥样硬化进展的影响时发现，p66Shc的小分子干扰RNA可通过抑制p66Shc的表达来减轻高S-腺苷同型半胱氨酸诱导的小鼠内皮血管舒缩反应损伤。另一项研究也表明，p66Shc的Ser36位点基因敲除大鼠对内皮素-1的反应受损，提示抑制p66Shc的表达可拮抗内皮素-1的血管收缩效应，减小血管张力，从而缓解MIRI[30]。此外，内皮功能受损后伴随的ROS水平升高和NO利用度下降可促进氧化型低密度脂蛋白（oxidized low-density lipoprotein，ox-LDL）增加，后者可在表观遗传层面通过抑制p66Shc启动子区甲基化和促进组蛋白-3乙酰化来增强p66Shc的表达，加重内皮功能受损[31]。总之，内皮细胞功能障碍可导致血管张力增加，且在降低内皮对NO生物利用度时增加p66Shc的活化，进一步加重内皮细胞功能障碍和MIRI，提示未来可通过靶向调控中间分子p66Shc来阻止MIRI相关的恶性循环。
3 基于p66Shc的治疗策略
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目前，调控衔接蛋白p66Shc的工具尚未成熟，但不少临床前研究已经取得了一定进展。最初，能活化p66Shc的蛋白激酶C-β（PKC-β）、蛋白激酶C-δ（PKC-δ）及c-Jun氨基末端激酶抑制剂（JNK）和肽基脯氨酰顺/反异构酶NIMA互作蛋白1（PIN1）被用于抑制p66Shc，但此类p66Shc特异性激活剂或抑制剂的调控实验均未取得理想效果，原因为p66Shc、p52Shc和p46Shc存在密切相关的多种亚型，这减少了p66Shc蛋白的靶区，缺乏p66Shc激活的独家信号机制是这一过程中的关键障碍[32]。而同时抑制这3种异构体可能会产生显著的有害后果，因为同时敲除小鼠的3种异构体具有胚胎致死性[33]。后来，基于表观遗传层面的研究取得了进展。Bock等[34]证实，活化蛋白C可通过对p66Shc启动子的表观遗传修饰使p66Shc表达沉默，减少ROS的生成及p66Shc向线粒体的转位。同样，研究发现，依赖烟酰胺腺嘌呤二核苷酸（NAD+）的沉默信息调节因子1（SIRT1）不仅能够抑制p66Shc的表达，而且可通过p66Shc的赖氨酸81位点去乙酰化破坏正常的p66Shc功能，减少血管内皮细胞中ROS的产生[35]。类似地，使用核桃酮抑制p66Shc转位至线粒体，能够减轻大鼠p66Shc介导的肠缺血再灌注损伤[36]。然而，以p66Shc为靶点的药物研发尚未取得明显进展，相关临床研究较少，一项正在进行的研究探讨了高强度间歇训练对心血管风险患者血管内皮功能的改善及对p66Shc表达和活性的下调作用（Cochrane，CN-01961852）。此外，随着基因治疗技术的迅猛发展，如果能够通过p66Shc基因的永久基因修饰而针对p66Shc进行特异性靶向治疗，可能具有巨大的治疗潜力。基因编辑的第3代技术CRISPR相关基因/蛋白质9（CRISPR-Cas9）系统的最新进展，为基因位点的靶向修饰应用于治疗人类疾病开启了新纪元[37]。如果能利用纳米颗粒或其他递送方法将p66Shc CH2结构域编码基因位点缺失的靶向构建物递送至患者心脏，或许能通过精准降低p66Shc蛋白的表达来缓解MIRI。
4 总结与展望
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IHD行再灌注治疗后的MIRI一直是困扰心血管病医师和患者的一大难题。包括氧化应激、炎症反应及血管内皮功能障碍在内的复杂机制已被广泛研究，但其确切机制尚未完全阐明。在独立疾病动物模型中进行的临床前实验显示药物等干预策略在减少MIRI损伤方面有益，但在临床转化时却往往以失败告终，部分原因可能是独立疾病动物模型无法模拟大多数IHD患者包括年龄、长期存在的慢性炎症及多种合并症在内的复杂自身条件[38]。衔接蛋白p66Shc广泛表达于哺乳动物除造血系统之外的大多数细胞中，已被证实可参与衰老、急慢性炎症、ROS产生、细胞骨架重组等不同生物学过程，在包括心血管疾病、糖尿病、代谢综合征及肿瘤在内的多种疾病中具有重要作用[9]。因此，在具有复杂机制的MIRI中研究衔接蛋白p66Shc的作用并探索基于p66Shc的治疗策略尤为重要。目前，基于p66Shc对包括MIRI在内的多种病理过程的靶向干预仍然具有广阔的研究空间，因此，需要更多的体内外研究来支持已知的分子机制，并进一步探索p66Shc在健康和疾病中的调控功能。
基金
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  • 国家自然科学基金(82060807)
文献
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参考文献 引证文献
排序方式：
[1]
Vardell E. Global health observatory data repository[J]. Med Ref Serv Q, 2020, 39(1): 67-74.
[2]
Safiri S, Karamzad N, Singh K, et al. Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990-2019[J]. Eur J Prev Cardiol, 2022, 29(2): 420-431.
[3]
Han LM, Luo XH, Zhao HL. Research progress on mechanism of autophagy regulatory factor mTOR in myocardial ischemia-reperfusion injury[J]. Med J Chin PLA, 2020, 45(11): 1161-1166.
[韩利民, 罗小红, 赵海龙. 自噬调控因子mTOR对心肌缺血再灌注损伤的作用机制研究进展[J]. 解放军医学杂志, 2020, 45(11): 1161-1166.]
[4]
Martins-Marques T, Hausenloy DJ, Sluijter JPG, et al.Intercellular communication in the heart: therapeutic opportunities for cardiac ischemia[J]. Trends Mol Med, 2021, 27(3): 248-262.
[5]
He J, Liu D, Zhao L, et al. Myocardial ischemia/reperfusion injury: mechanisms of injury and implications for management(Review)[J]. Exp Ther Med, 2022, 23(6): 430.
[6]
Jia L, Yang L, Tian Y, et al. Nrf2 participates in the protective effect of exogenous mitochondria against mitochondrial dysfunction in myocardial ischaemic and hypoxic injury[J]. Cell Signal, 2022, 92: 110266.
[7]
Boengler K, Bencsik P, Palóczi J, et al. Lack of contribution of p66shc and its mitochondrial translocation to ischemia-reperfusion injury and cardioprotection by ischemic preconditioning[J]. Front Physiol, 2017, 8: 733.
[8]
Wright KD, Staruschenko A, Sorokin A. Role of adaptor protein p66Shc in renal pathologies[J]. Am J Physiol Renal Physiol, 2018, 314(2): F143-F153.
[9]
Mir HA, Ali R, Mushtaq U, et al. Structure-functional implications of longevity protein p66Shc in health and disease[J]. Ageing Res Rev, 2020, 63: 101139.
[10]
Chen C, Liu H, Lin YG, et al. Research progress on the role of sarcopenia in the pathogenesis of atherosclerotic cardio-cerebrovascular disease in the elderly[J]. Med J Chin PLA, 2021, 46(5): 512-517.
[陈长, 刘辉, 蔺阳刚, 等. 肌少症在老年动脉粥样硬化性心血管疾病发病中的作用研究进展[J]. 解放军医学杂志, 2021, 46(5): 512-517.]
[11]
Hajam YA, Rani R, Ganie SY, et al. Oxidative stress in human pathology and aging: molecular mechanisms and perspectives[J].Cells, 2022, 11(3): 552.
[12]
Adameova A, Horvath C, Abdul-Ghani S, et al. Interplay of oxidative stress and necrosis-like cell death in cardiac ischemia/reperfusion injury: a focus on necroptosis[J]. Biomedicines, 2022, 10(1): 127.
[13]
Boengler K, Bornbaum J, Schlüter KD, et al. P66shc and its role in ischemic cardiovascular diseases[J]. Basic Res Cardiol, 2019, 114(4): 29.
[14]
Pacini S, Pellegrini M, Migliaccio E, et al. p66SHC promotes apoptosis and antagonizes mitogenic signaling in T cells[J]. Mol Cell Biol, 2004, 24(4): 1747-1757.
[15]
Migliaccio E, Giorgio M, Mele S, et al. The p66shc adaptor protein controls oxidative stress response and life span in mammals[J]. Nature, 1999, 402(6759): 309-313.
[16]
Veltman D, Wu M, Pokreisz P, et al. Clec4e-receptor signaling in myocardial repair after ischemia-reperfusion injury[J]. JACC Basic Transl Sci, 2021, 6(8): 631-646.
[17]
Yang YY, Deng RR, Chen Z, et al. Piperazine ferulate attenuates high glucose-induced mesangial cell injury via the regulation of p66Shc[J]. Mol Med Rep, 2021, 23(5): 374.
[18]
Zhang M, Xie Y, Yan R, et al. Curcumin ameliorates alveolar epithelial injury in a rat model of chronic obstructive pulmonary disease[J]. Life Sci, 2016, 164: 1-8.
[19]
Algoet M, Janssens S, Himmelreich U, et al. Myocardial ischemia-reperfusion injury and the influence of inflammation[J]. Trends Cardiovasc Med, 2022. doi: 10.1016/j.tcm.2022.02.005.
[20]
Zhao Y, Wang Z, Feng D, et al. p66Shc contributes to liver fibrosis through the regulation of mitochondrial reactive oxygen species[J]. Theranostics, 2019, 9(5): 1510-1522.
[21]
Kang IS, Kwon K. Potential application of biomimetic exosomes in cardiovascular disease: focused on ischemic heart disease[J].BMB Rep, 2022, 55(1): 30-38.
[22]
He JZ, Bellenger NG, Ludman AJ, et al. Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: promise, disappointment, and hope[J]. Rev Cardiovasc Med, 2022, 23(1): 23.
[23]
Botts SR, Fish JE, Howe KL. Dysfunctional vascular endothelium as a driver of atherosclerosis: emerging insights into pathogenesis and treatment[J]. Front Pharmacol, 2021, 12: 787541.
[24]
Griffiths K, Lee JJ, Frenneaux MP, et al. Nitrite and myocardial ischaemia reperfusion injury. Where are we now?[J]. Pharmacol Ther, 2021, 223: 107819.
[25]
Francia P, delli Gatti C, Bachschmid M, et al. Deletion of p66shc gene protects against age-related endothelial dysfunction[J].Circulation, 2004, 110(18): 2889-2895.
[26]
Shi Y, Savarese G, Perrone-Filardi P, et al. Enhanced age-dependent cerebrovascular dysfunction is mediated by adaptor protein p66Shc[J]. Int J Cardiol, 2014, 175(3): 446-450.
[27]
Yamamori T, White AR, Mattagajasingh I, et al. P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction[J]. J Mol Cell Cardiol, 2005, 39(6): 992-995.
[28]
Spescha RD, Glanzmann M, Simic B, et al. Adaptor protein p66(Shc) mediates hypertension-associated, cyclic stretch-dependent, endothelial damage[J]. Hypertension, 2014, 64(2): 347-353.
[29]
Xiao Y, Xia J, Cheng J, et al. Inhibition of S-adenosylhomo-cysteine hydrolase induces endothelial dysfunction via epigenetic regulation of p66shc-mediated oxidative stress pathway[J].Circulation, 2019, 139(19): 2260-2277.
[30]
Miller B, Palygin O, Rufanova VA, et al. p66Shc regulates renal vascular tone in hypertension-induced nephropathy[J]. J Clin Invest, 2016, 126(7): 2533-2546.
[31]
Kim YR, Kim CS, Naqvi A, et al. Epigenetic upregulation of p66shc mediates low-density lipoprotein cholesterol-induced endothelial cell dysfunction[J]. Am J Physiol Heart Circ Physiol, 2012, 303(2): H189-H196.
[32]
Kumar S. P66Shc and vascular endothelial function[J]. Biosci Rep, 2019, 39(4): BSR20182134.
[33]
Lai KM, Pawson T. The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo[J].Genes Dev, 2000, 14(9): 1132-1145.
[34]
Bock F, Shahzad K, Vergnolle N, et al. Activated protein C based therapeutic strategies in chronic diseases[J]. Thromb Haemost, 2014, 111(4): 610-617.
[35]
Kumar S, Kim YR, Vikram A, et al. Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction[J]. Proc Natl Acad Sci U S A, 2017, 114(7): 1714-1719.
[36]
Feng D, Yao J, Wang G, et al. Inhibition of p66Shc-mediated mitochondrial apoptosis via targeting prolyl-isomerase Pin1 attenuates intestinal ischemia/reperfusion injury in rats[J]. Clin Sci (Lond), 2017, 131(8): 759-773.
[37]
Zaib S, Saleem MA, Khan I. CRISPR-Cas9 genome engineering: trends in medicine and health[J]. Mini Rev Med Chem, 2022, 22(3): 410-421.
[38]
Samaja M, Pagliaro P. Long and narrow road to win over myocardial ischemia-reperfusion injury[J]. Trends Cardiovasc Med, 2022. doi: 10.1016/j.tcm.2022.02.013.
2023年第48卷第4期
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doi: 10.11855/j.issn.0577-7402.2022.04.0456
  • 接收时间：2022-04-15
  • 首发时间：2025-12-03
  • 出版时间：2023-04-28
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  • 收稿日期：2022-04-15
  • 录用日期：2022-06-28
基金
National Natural Science Foundation of China(82060807)
国家自然科学基金(82060807)
作者信息
    1兰州大学第一临床医学院，甘肃兰州 730000
    2兰州大学第一医院心脏中心，甘肃兰州 730000
    3甘肃省心血管病重点实验室，甘肃兰州 730000

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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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