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近期感染急性脑梗死中医证型探讨及其与炎性反应因子的研究
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摘要
研究目的:①通过对近期感染急性脑梗死患者的中医证候进行横断面调查,探讨近期感染急性脑梗死的中医证候分布,为寻找近期感染急性脑梗死的中医证侯变化规律,制定防范措施提供依据。②在近期感染急性脑梗死疾病中,炎性反应因子相互调控,参与了脑梗死病急性期的血液循环、血管的病理变化过程。我们假定炎性反应还参与了近期感染急性脑梗死患者的中医证候的形成。调查近期感染急性脑梗死患者的炎性反应因子与其中医证候的相关性,从而探讨近期感染急性脑梗死患者中医证候形成的生物学基础,从而为证候研究的客观化提供理论依据。
     研究方法:①理论探讨:回顾脑梗塞(中风)现代医学研究和中医证候研究概况,中风中医证候分布及演变规律,并探讨中风中医证候与相关的因素的研究进展。②确定急性脑梗塞中西医诊疗标准,研究对象的纳入和排除标准,采取横断面调查的方式,确定研究对象为92例近期感染急性脑梗死患者,采集92例患者的一般情况、阶段信息、中医四诊信息实验室检测结果等资料。由严格培训的专业人员,对研究对象集中进行统一的证候评价,将结果录入数据库。③按中风病辨证诊断标准,将92例近期感染急性脑梗死患者分类,即将收集的病例分为风、火、痰、瘀、气虚、阴虚六型。④采集全部病例的血液标本;每例病例抽取空腹静脉血6ml,用促凝管收集、立即派专人送往实验室,离心3000r∕min分离血清,放入-80℃的冰箱保存,最后进行统一检测,所有过程均严格执行无菌操作,采用酶联免疫吸附双抗体夹心法(ELISA)检测血清IL-1β、TGF-β、sICAM-l、sEPCR、MMP-9的含量,实验过程在湖北中医药大学昙华林校区实验室完成测定,所有操作均按说明书要求进行。将所检测的结果集中收集录入数据库。统计分析将采用SPSS13.0统计分析软件进行计算,不同组的计量资料采用x±s进行统计描述,采用t检验比较组间差异。P<0.05认为差别有统计学意义。计数资料使用频数表(构成比)进行统计描述。炎性反应因子与证候要素的相关性采用相关性检验的方法。
     结果:①92例研究对象总体上以气虚证、痰证、火证出现频率最高。经分析,结合各证候要素在近期感染急性脑梗死患者中所占比例(气虚证53.3%、痰证45.7%、火证42.4%),可见,近期感染急性脑梗死患者主要证候表现均为气虚证、痰证、火热证。②研究对象中表现为一证独见和二证并见的比例最高,分别是42.4%、35.9%。一证独见的患者中,以“气虚”、“痰”和“火热”型最多,分别占33.3%、28.2%、25.6%;二证并见的,以“痰+气虚”型最多,是42.4%,其次是“火热+气虚”型和“风+火热”型,分别占18.2%,12.1%。③炎性反应因子IL-1β含量在火证中明显高于非火热证型,经t检验P<0.05,差别有统计学意义,并且IL-1β含量在气虚证组明显高于非气虚证组,经t检验P<0.05,差别有统计学意义;相关性分析结果,火证、气虚证与IL-1β水平相关,P<0.01,有统计学意义;④炎性反应因子TGF-β含量在痰证中高于非痰证,经t检验P<0.05,差别有统计学意义,相关性分析结果,痰证与TGF-β水平正相关,P<0.01,瘀证与TGF-β水平负相关,P<0.01有统计学意义。⑤炎性反应因子sICAM-1含量在瘀证中明显高于非瘀证型,经t检P<0.05,差别有统计学意义,sICAM-1含量在痰证中高于非痰证,经t检验P<0.05,差别有统计学意义;相关性分析结果,瘀证、痰证与sICAM-1水平正相关,P<0.01,有统计学意义;⑥炎性反应因子MMP-9、sEPCR含量在血瘀证明显高于非血瘀证,经t检验P<0.05,差别有统计学意义,相关性分析结果,瘀证与MMP-9、sEPCR水平正相关P<0.01,有统计学意义。
     结论:①近期感染急性脑梗死的患者以气虚、痰、火为主要证候表现,证候要素的组合较为简单,多表现为气虚、痰、火的单独出现或几个证型相互组合;②近期感染急性脑梗死的患者血液中细胞白介素-1β(IL-lβ)的含量变化与火证、气虚证之间有明显的相关性,可能成为判定火证、气虚证的指标之一;③近期感染急性脑梗死的患者血液中转化生长因子β(TGF-β)的含量变化与痰证有相关性,与瘀证负相关,可能成为判定痰证和瘀证的指标之一;④近期感染急性脑梗死的患者血液中可溶性细胞粘附因子-1(sICAM-1)的含量变化与瘀血证、痰证有明显的相关性,可能成为判定瘀血证、痰证的指标之一。⑤近期感染急性脑梗死的患者血液中可容性细胞蛋白C(sEPCR)、金属蛋白酶9(MMP-9)的含量变化与瘀血证有明显的相关性,可能成为判定瘀血证指标之一。
Objective:①Through the cross-sectional survey of recent infection inpatients with acute cerebral infarction TCM Syndrome, Discussion onrecent infection in acute cerebral infarction TCM syndrome distribution,for the TCM syndrome changes of recent infection of acute cerebralinfarction, provide the basis for the formulation of preventive measures;②In the recent infection disease of acute cerebral infarction,Inflammatory cytokine regulation, pathological changes in bloodcirculation, with cerebral vascular disease period,We assume that theinflammatory reaction formation of recent infection in patients with acutecerebral infarction TCM syndrome also participate in, Investigation ofrelationship between recent infection in patients with acute cerebralinfarction and inflammatory factor and syndrome of traditional Chinesemedicine, To explore the biological basis of recent infection syndromein patients with acute cerebral infarction patterns formed, whichprovided a theoretical foundation for the research of the objectificationof syndrome.
     Methods:①Theoretical study:Review of research on brain infarction ofmodern medicine and TCM Syndrome Study, And the evolution rules of distribution of TCM Syndromes of apoplexy, And discusses theresearch progress of TCM syndrome of stroke and related factors;②Determination of Western medicine diagnosis standard of acutecerebral infarction, The object of study inclusion and exclusion criteria,Cross-sectional survey method, To determine the object of study for92cases of infection in patients with acute cerebral infarction, In general,phase information and information of four diagnostic methods, data of92patients, By the strict training of professionals, the object of study,mainly syndromes evaluation are unified, the results into the database;③Blood samples were collected for all patients, Each case of fastingvenous blood were extracted by6mlprocoagulant andcollection,immediately delivered Laboratory,Centrifugal separatingserum3000r/min,-80℃preservation, unified examination, allprocesses are strict sterile manipulation, Using enzyme-linkedimmunosorbent assay (ELISA) for detection of serum antibodysandwich method IL-1β、TGF-β、slCAM-l、sEPCR、MMP-9, All theoperation requirements according to the instructions, The collected datais collected into the database. Statistical analysis using SPSS13.0statistical analysis software for calculation, Measurement data bydifferent groups for statistical description use x±s, The differencebetween the group use t test. P<0.05,That difference was significant,Count data using frequency tables (ratio) of statistical description, By using the method of correlation analysis of the correlation betweeninflammatory factors and syndrome elements
     Results:①92subjects in general Qi, phlegm syndrome, heatsyndrome had the highest frequency, Through the analysis, combinedwith the syndrome factors of infection ratio in patients with acutecerebral infarction in the near future(Qi deficiency, phlegm fire45.7%,53.3%,42.4%),Visible, recent infection in patients with acute cerebralinfarction and the main symptoms were Qi-deficiency, phlegmsyndrome, heat syndrome;②The research object of performance for asingle syndrome and two cards and the highest proportion, respectivelyis42.4%,35.9%,A certificate of the patients, the "Qi","phlegm" and"hot" type is the most, accounting for33.3%,28.2%,25.6%respectively,Two cards and see, most in the "phlegm+Qi",42.4%, Thesecond is "hot+Qi" and "air+hot" type, accounted for18.2%,12.1%.③Inflammatory factors of IL-1β content in fire syndrome wassignificantly higher than that of non-heat syndromes, testing by tP<0.05,The difference was significant. And the IL-1β content in the Qideficiency syndrome group was significantly higher than that in non-qideficiency syndrome group,testing by t P<0.05,The difference wassignificant. Results of correlation analysis:Fire syndrome, Qi deficiencysyndrome associated with the level of IL-1β, P<0.01, there was statistical significance.④Inflammatory factors of TGF-β were higherthan that of non-phlegm syndrome in phlegm syndrome,testing by tP<0.05,The difference was significant. Results of correlation analysis:Phlegm syndrome associated with the levels of TGF-β, P<0.01,Negative correlation between blood stasis syndrome and the level ofTGF-β, P<0.01had statistical significanc⑤Inflammatory factors andsICAM-1content in blood stasis syndrome was significantly higher thanthat of non blood stasis syndrome,By t P<0.05, the difference wassignificant,The content of sICAM-1is higher than that of non-phlegmsyndrome,Testing by t P<0.05, the difference was significant,Resultsof correlation analysis:Syndrome of blood stasis, phlegm syndromeand the level of sICAM-1positive correlation, P<0.01, there wasstatistical significance。⑥Inflammatory factors MMP-9, sEPCR contentin the blood were significantly higher than that of blood stasissyndrome,Testing by t P<0.05, the difference was significant,Resultsof correlation analysis:Positive correlation with MMP-9, sEPCR levelsin blood stasis syndrome P<0.01, there was statistical significance.
     Conclusion:①The recent infection in patients with acute cerebralinfarction with Qi deficiency, phlegm, fire as the main symptoms,combination of syndrome elements of more complex, Moreperformance for the separate Qi, phlegm, fire or some type of syndrome combination;②Recent interleukin infection of acute cerebral infarctionin patients with (IL-lβ) there were significant correlations between thecontent changes and fire syndrome, Qi deficiency, may become one ofthe indexes for judging the fire syndrome, Qi deficiency syndrome;③Recent infection of acute cerebral infarction in patients withtransforming growth factorβ (TGF-β) were correlated with the changesof the content of phlegm syndro,Associated with blood stasis syndromenegative, may become one of the indexes for judging the phlegm andblood stasis.④The soluble cell adhesion infection in acute cerebralinfarction in patients with factor-1(sICAM-1) were significantlycorrelated with the content changes of blood stasis, phlegm, could beone of the index of blood stasis, phlegm syndrome⑤Recent infection ofacute cerebral infarction patients with blood compatibility of cell proteinC (sEPCR), matrix metalloproteinase9(MMP-9) content changes had asignificantcorrelation with blood stasis syndrome, blood stasis may beone of the index determination.
引文
[1]邢成名.缺血性脑血管病[M].人民卫生出版社.2003,3:75-95.
    [2]Demolis P Carville C,Giudicelli JF.Effects of an angiotensin一converting emzynze inhibitor lisinoPril,on cerebral blood flowautoregulation in healthy volunteers.J Cardiovasc Pharmaeol,1993,22:373.
    [3]Anonymous:4th Ameriean College of Chest Physicians ConsensusConferenee on Antithrombotic TheraPy. Tueson, Arizona April1995.Proceedings [seeeomments].[Review].Chest1995:108:2255-5225.
    [4]TanneD,Goldbourt U,Zion M.Reicher-ReissH, KaPlinsky E, BeharS:Frequeney and Prognosis of stroke/TIA among4808survivors ofacute myoeardial infaretion.The SPRINT Study Group.Stroke,1993:24:1490-1495.
    [5]BodenheimerMM,SauerD,ShareefB,BrownMW,FleissJL,MossAJ:Relation between Myoeardial infarct loeation and stroke [see eomments].Journal of the American College of Cardiology,1994:24:61-66.
    [6]DexterDJ,etal.The assoeiation of stroke and eoronary heartdisease:aPoPulation study.Mayo Clinic Proceedings,1987:62:1077-1083.
    [7]徐安定,陈明星.脑血管病的三级预防[J].广东医学.2002,23(6):23-25.
    [8]UK Prospectve Diabetes Study Group.Intensive blood-glueosecontro1with sulphonylureas or insulin compared with conventionaltreatment and risk of cornplications in patients with type2diabetes.Lancet,1998,352:837
    [9]Henry J.M.Barnett,J.P.Mohr,BennettM.stein,Frank M.Yatsu.卒中病理生理诊断及其治疗[J].沈阳:辽宁科学技术出版社.2001:149
    [10]Hoballah JJ,etal.Entering the ninth decade is not a contraindie-ation for carotid Endartereetomy. Angiolog.1998,49(4):275-278.
    [11]PilliPB.etal.首次卒中的预防:有关指南的审查以及全国卒中协会额共识报告.美国医学会杂志中文版.1999,-8(6):304-308.
    [12]LIPtonP,etal.Mechanism of intracellular caleium accumulation in theCAI region of rat hippoeampus during anoxia in vitro.Stroke.1990,21:60.
    [13]郝建东,朱长庚,刘庆莹等.地塞米松对谷氨酸升高海马神经元胞内钙作用的影响[J].神经解剖学杂志.1999,15(3):528.
    [14]BiekerPE,etal.DeveloPment changes intracellular caleium regul-ation in rats cerebral cortex during hyPoxia,J Cereb Blood FlowMetab,1993,13(5):811.
    [15]Caow,etal.Oxygen free radical involvement in isehemia andreporusing injury to brain.Neurosei Lett.1980,88(2):233.
    [16]LiXJ,Zhang LM,GuJ,etal、Melatonin decreases Produetion ofhydroxyl radical during Cerebral isehemia rePerfusion.ActaPharmacol Sin,1997,18(5):39.
    [17]Mukherjee SK,etal.APoPtosis and DNA framentation as induced byterritiary but lyhydroPeroxide In the brain.Brain Res Bull.1995,38(6):595.
    [18]TroyCM,etal.Down regulation of coPPer/zinc superoxide Dismuta-ses apoptotic death in PCI2neuronal cell.Pro Natl Acd Sci USA.1994,91(4):6384.
    [19]MatsuyamaT,etal.Fas antigan mRNA induction inPostischemic mur-ine brain.Brain Res.1994,657:342.
    [20]HossannKA,Viability threshold and the Penumbra of focialisehemia.Ann Neurol,1994,36:557~565.
    [21]SiesjioBK,etal.Role and mechanisms of secondary mintoehon-drial failure.Acta Neurochir1999,73:7-13.
    [22]HossmannKA,.Periin farct dePolarizations.Cerebrovasc BrainMetab Rev.1996,8:195-208.
    [23]MiesG,etal.Correlation between Peri-infarct DC shifts and isehemicneuronal damage in rats.NeurorePort.1993,4:709-711.
    [24]O Neill LA,NF-kappa B:a crucial transcription factor for glial andneuronal cell function.Trends Neurosei.1997-20(6):252-258.
    [25]IadeeolaC,etal.The transcription factor interferon regulatoryfactor1is expressed after cerebral isehemia and contributes toischernic brain injury,JExP Med.1999,189(4):719-727.
    [26]Planas AM,etal.Induetion of stat3,a signal transducer andteanscreption factor inreactive Mieroglia following transeientfocal ceredral isehemia.Eur J Neurosei.1996,8(12):2612-2618.
    [27]RothwellNJ,etal.Cytokines and the nervous system2: Actions andmechanisms of action.Trends Neurosci.1995,18:130-136.
    [28]KroemerG,etal.Mitochondrial contral of apoptosis.ImmunolToday.1997,18(l):44-45.
    [29]KroemerG,etal.Mitochondrial contra1of apoptosis.Immunoltoday.1997,18(1):55-56.
    [30]GreenDR,etal.Mitoehondria and apoptosis. Science.l998,281(5381):1309-1312.
    [31]KristianT,etal.Calcium in ischemic cell death. Stroke.1996,27(2):327-332.
    [32]Nieminen AL,etal.Cyclosporin A delays mitochondrial depolariz-ation induced by N-methyl-D-aspartate in cortical neurons:evidenc-eof the mintochondrial Permeability transition.Neurosciene.1996,75(4):993-997.
    [33]Neumar RW,.Molecular mechanisms of ischemic neuronal injuryAnn Emerg Med.2000,36(5):483-506.
    [34]LeistM,etal.Apoptosis,excitotoxicity,and neuropathlogy. ExP CellRes.1998,239(2):183-201.
    [35]FinkKetal.Prolonged therapeutic window for ischemic brain dama-ge caused by delayed caspase activation.J Cereb Blood Flow Metab.1998,18:1071-1076.
    [36]内经[M],北京:科学技术文献出版社,1996,1:181.
    [37]内经[M],北京:科学技术文献出版社,1996,1:113.
    [38]福州市人民医院校释.脉经校释[M],北京:人民卫生出社,1984,1:7.
    [39]何裕民,刘文龙.新编中医基础理论[M].北京:北京医科大学、中国协和医科大学联合出版社,1996:13.
    [40]匡调元.论辨证与辨体质[J].中国中医基础医学志,2002,8(2):81-85.
    [41]郭蕾.证候概念渊源及现代对证候的研究简析[J].中医药学刊,2003,21(6):947-948.
    [42]秦伯未.中医“辨证论治”概说[J].江苏中医,1957,(1):2.
    [43]会议秘书组.全国中医病名与证候规范化研讨会议述要[J].中国医药学报,1990,(5):3.
    [44]郭蕾,王永炎,王志斌.关于证候概念的诠释[J].北京中医药大学学报,2003,26(2):5-8.
    [45]清.王清任.医林改错[M],上海:上海科学技术出版社,1966,1:25.
    [46]清.沈金鳌.杂病源流犀烛[M],北京:人民卫生出版社,2006,1:364.
    [47]林建雄,冯哗,陈建霖等.中风病急性期中医证候分布分析[J].北京中医药大学学报,2004,27(4):83.
    [48]刘金民.251例急性期中风病证候的病理学基础分析[J].北京中医药大学学报,1994,17(4):30.
    [49]王顺道,杜梦华,解庆凡等.中风病急性期证候演变规律的研究[J].中国中医急证,1996,5(3):121.
    [50]王顺道,任占利,杜梦华等.中风病始发态证候发生与组合规律的临床研究[J].中国中医急证,1996,5(3):12.
    [51]张聪.从病机看中风病证候要素[J].中华中医药刊,2007,25(3):468-469.
    [52]王永炎,张启明,张志斌.证候要素及其靶位的提取[J].山东中医药大学学报,2006,30(l):6-7.
    [53]王顺道,任占利,杜梦华,等.中风病始发态证候发生与组合规律的临床研究[J].中国医药学报,1996,11(3):17-20.
    [54]王顺道,司志国,黄宜兴,等.中风病证候的初步研究[J].中国中医急证,1995,4(2);85-88.
    [55]杨利,黄燕,蔡业峰,等.1418例中风患者痰瘀证候分布和演变规律探析[J].辽宁中医杂志,2004,31(6):459-460.
    [56]马斌,高颖.中风病发病第7天证候要素的初步分析[J].中国中医基础医学杂志.2006,12(7):494-496.
    [57]马斌,高颖.中风病发病第7天和第14天证候要素演变规律初步研究[J].辽宁中医杂志.2006,33(12):1561-1563.
    [58]王顺道,杜梦华,解庆凡等.中风病急性期证候演变规律的研究[J].中国中医急证,1996,5(3):12.
    [59]余学庆,李建生,庆慧.中风病证候影响因素的研究[J].新中医,2003,35(11):20-22.
    [60]王大忠.中风病证候分布与影响因素关系探讨[J].医药论坛杂志,2005,26(18):67-68.
    [61]黄燕,缪晓路,蔡业峰,等.缺血性中风急性期证候不同地域差异性分析[J].中国中医基础医学杂志,2008,14(3):207-20.
    [62]梁伟雄,赖世隆,刘茂才,等.中风病中医证候与相关因素的分析[J].广州中医药大学学报,1999,16(2):81.
    [63]王顺道,任占利,杜梦华,等.中风病始发态证候影响因素的研究[J].北京中医药大学学报,1996,19(4):43.
    [64]林建雄,冯哗,高颖等.中风病急性期火热证与西医诊察指标相关性研究[J].北京中医药大学学报,2004,27(5):77.
    [65]孙志华.缺血性脑血管病与炎性免疫因子[J].医学述,2007,13(16):1217-1219.
    [66]VilanN,CastilloJ,DavolosA,etal.Proinflamatory cytokines and earlyneurological worsening in isehemic stroke. Stroke,2000,31(10):2325-2329.
    [67]瞿浩,刘强.脑梗死患者血浆IL-1β、IL-6含量变化及临床意义[J].贵州医药,2002,26(7):657-658.
    [68]毕国荣,宋利春.脑梗死患者恢复期脑组织血浆肿瘤坏死因子-a、白介素-lβ含量变化[J].现代康复,2001,5(6):57-58.
    [69]杜凯音,董莉,孙喜山.中风中医辨证分型与血清工L-6关系的研究[J].吉林中医药,2003,23(9):5-6.
    [70]梁浩荣,湛剑飞,宋颖.中风中脏腑痰热内闭心窍证型与细胞免疫因子变化的关系研究[J].放射免疫学杂志,2000,13(6):329-330.
    [71]关少侠,湛剑飞,丁萍.急性缺血性中风始发状态风证与免疫细胞因子的关系研究[J].中西医结合杂志,2001,11(5):266-268.
    [72]梁晖,陈少芳.出血性中风中经络血清sICAMsel、MDA变化的临床研究[J].福建中医学院学报,2005,15(6):3-5.
    [73]祝美珍,李志刚.缺血性中风中医辨证分型与ICAM-1和CD62P表达水平的相关性[J].中国中西医结合杂志,2005,25(3):225-227.
    [74]黄晓.缺血性中风(中经络)证候分类与血脂、血压、血液流变学关系的研究[J].中国中医急证,2002,11(l):32-33.
    [1]第四届全国脑血管病会议修订的标准(1995).中华神经科杂志.1996;29(6):376-381.
    [2]国家中医药管理局脑病急证科研组起草制定,中风病诊断疗效评定标准(试行).北京中医药大学学报,1995;19(1):55-56.
    [3]国家中医药管理局脑病急证科研组制定,中风病辩证诊断标准(试行).北京中医药大学学报,1994;17(3):64-66.
    [4]Wang ZF,Tang LL,Yah H,et a1.Effects of huperzine A on memorydeficits and neurotrophic factors production after train sient cerebralischemia and reperfusion in mice[J].Pharmacol Bioehem Behav,2006,83(4):603-611.
    [5]中国高血压防治指南.中华心血管病杂志,2011,39(7):579-616.
    [6]卫生部疾病控制司.《中国糖尿病防治指南》.中国糖尿病杂志,2012,20(1):283-285.
    [7]中国成人血脂异常防治指南制订联合委员会.中国成人血脂异常防治指南.中华心血管病杂志,2007,35(5):390-419.
    [1]王苏.缺血性脑血管病的其他危险因素[J].脑与神经疾病杂志.2002,10(4):652.
    [2]郑悦,桂冰.近期感染和缺血性脑中风的关系探讨[J].辽宁医学杂志,2003,17(4):102.
    [3]彭华,郭洪志.缺血性脑血管病的新独立危险因素研究进展[J].脑与神经疾病杂志.2003,11(6):386.
    [4]范俊林,赵世刚.脑血管病危险因素研究进展[J].内蒙古医学杂志.2010,42(4):436.
    [5]SaitoK,Suyama K,Nishida K,et a1.Early increases in TNF-a,IL-6andIL-l β levels following transient cerebral ischemia in gerbilbrain.NeurosciLett,1996,206(2);149-150.
    [6]Mathiesen T,Andersson B,Loftenius A,eta1.Inereased interleakin-6levels in cerebrospinal fluid following Subaracbnoidhemorrhage.JNeurosurg,1993,78(4);562.
    [7]SchettniG,Grimalai M,Landilfie,eta1.Role of interleakin-6in theneuroendocrine system.ActaNeurol,1991,24(13);316.
    [8]Touzani0,Boutin H,ChuquetJ,eta1.Potential mechanisms of inter-leukin-1involvement in cerebral ischaemia.J Neuroimmunol,1999,100;203-215.
    [9]Zheng GZ,MichaelC,AntonG.Cerebral vessels express Interleukin-1βafter focal cerebral ischemia[J].Brain Research,1998,784;210—217.
    [10]NikolaosK,PiaK,YuminH,eta1.Ischemia stroke is associatedwith a systemic increase of blood mononuclear ceils expressinginterleukirr8mRNA[J].Stroke,1998,29:462-466.
    [11]Zhai QH,Futrell N,Hen FJ.Gene expression of IL-1βIn relations-hip to TNF-alpha.IL-lbeta andIL-2in the rat brain Following middl-e cerebral artery occlusion[J].Neurol Sci,1997,152;119—124.
    [12]Buttini M,Appel K,SauterA,eta1.Expression of tumor Necrosisfactor alpha after focal cerebral ischemia in the rat[J].Neuroscien–ee,1996,71:1-16.
    [13]毕国荣,卢丽萍,剑非.动态观察急性脑血管病患者血浆肿瘤坏死因子-α含量变化的临床意义[J].临床神经病学杂志,1999,12(2);86—87.
    [14]黄作毅,韩凤,吴军.急性脑血管病患者血浆TNF、IL-6含量研究[J].中风与神经疾病杂志,1999,16(2):103—104.
    [15]Lehxm ann E,et al,Microglia and macrophages are majorSourcesoflocally proced transforming growth factor-betal after transientmiddle cerebral artery occlusion in rats.G1ia,1998,24(4);437—438.
    [16]Krupinski J,KumarP。Kumar S,eta1.Increased expression of TGF-beta1in brain tissue after ischemic stroke inhumans[J].Stroke,1996,27(5);852—857.
    [17]IntisoD,ZarrelliMM,LagioiaG,Di Rienzo F,Checchia DeambrosioC,Simone P,Tonali P,Cioffi Dagger RP.Tumor necrosis Factor alplaserumlevels and inflammatory response in acute ischemic strokepatients.Neurol Sci,2004,24(6);390—396.
    [18]杜凯音,董莉,孙喜山.中风中医辨证分型与血清IL-6关系的研究[J].吉林中医药,2003,23(9):5-6.
    [19]梁浩荣,湛剑飞,宋颖.中风中脏腑痰热内闭心窍证型与细胞免疫因子变化的关系研究[J].放射免疫学杂志,2000,13(6):329-330.
    [20]关少侠,湛剑飞,丁萍.急性缺血性中风始发状态风证与免疫细胞因子的关系研究[J].中西医结合杂志,2001,11(5):266-268.
    [21]湛剑飞,关少侠,马雅玲,等.急性脑梗死始发状态证候量值与神经内分泌免疫网络功能指标水平的相关性探讨[J].中国中西医结合急救杂志,2002,9(2):81-83.
    [22]刘立峰,刘玉和,沈维高,等.白细胞介素-1的结构、来源、分布、功能及其与疾病的关系[J].华北大学学报.2006,10(5):7.
    [23]易兴阳,袁光固,周东,等.脑梗死患者周围血细胞因子研究[J].中风与神经疾病杂志,1996,13(6);333-335.
    [24]易兴阳,潘继豹,池丽芬,等.进展性缺血性脑卒中患者细胞因子及黏附分子的研究[J].中国神经免疫学和神经病学杂志,2006,13(3)169-172.
    [25]叶心国,李承晏,毛善平.急性脑梗死患者血清TNF-α、IL-l和slCAM-1含量变化[J].中华急诊医学杂志,2003,12(1);32-34.
    [26]王建茹,冯忠军,李娜,等.急性脑梗塞患者血IL-1、IL-6、TNF、TM水平的变化及临床意义[J].中国免疫学杂志,2004,20(6);431-432.
    [27]Frank CB,Raymond FW,PatriciaAS,et a1.IschemicpreconditioningAndbrain tolerance[J].Stroke,1998,29;1937-1951.
    [28]Krupinski J,Kumar P,Kumar S,et a1.Increased expression of TGF-beta l in brain tissueafterischemicstroke inhumans [J].Stroke,1996,27(5);852-857.
    [29]程利萍,贾建民,濮盂久.IL-1β、TNF-α、TGF-β1与缺血性脑损害相关性研究[J].中国神经免疫学和神经病学杂志,2004,11(1):36-38.
    [30]何志义,欧阳巅,张强,等.老年急性脑血管病患者细胞因子及其受体的研究[J].中华老年心脑血管病杂志,2001,3(5);322-325.
    [31]王钢,黄建群.脑卒中患者转化生长因子与细胞粘附因子检测及分析[J].中华内科杂志,2000,39(5):309-311.
    [32]郭正良,傅毅,辛晓瑜,等.急性脑梗死患者ox-LDL、TGF-βl和vcAM-l的检测[J].上海交通大学学报(医学版),2006,26(11);1274-1276.
    [33]Lehxm ann E,eta1.Microglia and macrophages axe major sourcesof locally proced transforming growth factor-betal after transientmiddle cerebral artery occlusion in rats.G1ia,1998,24(4):437-438.
    [34]KawamataT,Ren J,ChanTC.Intracisternal osteogenic Protein-lenhances functionalrecovery folowingfoca stoke.Neuroreport,1998,9(7);1441-1445.
    [35]Lehxm ann E,et a1.Microglia and macrophages axe major sourcesof locally proced transforming growth factor-betal after transient middlecerebral artery occlusion in rats.G1ia,2008,24(4):437-438.
    [36]blallatZ,GojovaA,Marahiol-FournigaultC,et a1.Inhibition oftransforming growth factor-beta Signaling accelerates atherosaler-osisand induces an unstable plaque phenotype in mice[J].Circ Res,2001,89(10):930-934.
    [37]Argmann: A, Van Den Diepstraten CH, Sawyez CG, eta1.Transforming growth factor-βl inhibits macrophage aholesteryl esteraccumulati-on induced by native and OX-idized VLDLremnants.Arterioscler Throm Vasc Biol,2001,21(12);2011-2018.
    [38]SaiuraA.SataM.HirataY,eta1.Tranilast inhibits transplant-associated coronary arteriosclerosisin amurine model of cardiac:transplantation[J].Eur J Pharmacol,2001,433(2—3);163—168.
    [39]Chen X,Ren S,MabiG,et a1.Hirulog-like peptide reduces restenos-is and expression of tissue factor and transforming growth factor-betain carotid artery of atherosolerotic rabbits[J].Atherosoleros-is,2009,169(1);31-40.
    [40]金惠铭,卢健,殷莲华.细胞分子病理生理学[M].郑州大学出版社,2002,110-125.
    [41]袁肇凯,黄献平,谭光波,等.冠心病血瘀证血管内皮细胞功能的检测分析[J].中国中西医结合杂志,2006,26(5):407-410.
    [42]胡小勤,陈利国.血管内皮细胞粘附分子与血瘀证相关性探讨[J].陕西中医,2005,26(3);249-250.
    [43]WuY.ZhuBD.Effectof Danggui BuxueDecoctionon proliferationAnd expression of intercellular adhesion molecule1in human umbilicalvein endothelial cells[J].J West China UnivbledSci(华西医科大学学报),2001,32(4);593—595.
    [44]Zhang Y J,Zhao LG,WuX Z.Effect of Huoxuehuayu Decoction onExpression of adhesive molecular of intrapulmonic endothelial cell ofrats suffered from SAP[J].Chin Tradit Herb Drugs(中草药),2001,32(11);1010-1011.
    [45]HaoY,Oiu Q Y,WJ.Effect of astragalus polysaccharin(APS) onYmphocyte-endothelium adhesion and the molecular mechanism[J].Immunnol J(免疫学杂志),2000,16(3);206-209.
    [46]陈利国,屈援,葛红颖,等.补阳还五汤对血瘀证大鼠血管内皮细胞粘附分子表达的影响[J].ChineseTraditional and Herbal Drugs(中草药),2005,36(5):706-709.
    [47]Esmon CT.The protein C anticoagulant pathway.ArteriosclerThromb,1992,12:135-145.
    [48]Esmon CT.The protein C pathway.Chest,2003,124:26-32.
    [49]EsmonCT.inflammationandthrombosis.JThrombHaemost.2003;1:1343-1348.
    [50]Esmon CT. The endothelial cell protein C receptor. ThrombHaemost,2000,83:639-643.
    [51]Esmon CT, Ding W, Yasuhiro K, et al. The protein C pathway: newinsights. Thromb Haemost,1997,78:70-74
    [52]Xu J, Esmon NL, Esmon CT. Reconstitution of the humanendothelia-l cell protein C receptor with thrombomodulin inphosphatidylcholi-ne vesicles enhances protein C activation. J BiolChem,1999,274:6704-6710.
    [53] Fay PJ,Smudzin TM,Walker FJ.Activated protein C-catalyzed ina-ctivation of human factor Ⅷ and factor Ⅶ a.Identification ofcleavage sites and correlation of proteolysis with cofactor activityl.J BiolChem,1991,266:20139-20145.
    [54] Bae JS,Yang L,Rezaie AR.Receptors of the protein C activationand activated proteinC signaling pathways are colocalized in lipid raftsof endothelial cells. Proc Natl Acad Sci USA,2007,104(8):2867-2872.
    [55]Liaw PC, Neuenschwander PF, Smirnov MD, et al. Mechanisms bywhich soluble endothelial cell protein C receptor modulates protein Cand activated protein C function.J Biol Chem,2000,275:5447-5452.
    [56]Regan LW,Stearns-Kurosawa DJ, Kurosawa S,et al.The endothelialcell protein Creceptor:inhibition of activated protein C anticoagu-lantfunction without modulation of reaction with proteinase inhibitors.J BiolChem,1996,271:17499-17503.
    [57]Saposnik B, Reny JL, Gaussem P, etal. A haplotype of the EPCRgene is associated with increased plasma levels of sEPCR and is acandidate risk factor for thrombosis.Blood.2004,103(4):1311-1318.
    [58]Uitte de Willige S,Van Marion V,Rosendaal FR,etal.Haplotypes ofthe EPCR gene,plasma sEPCR levels and the risk of deep venousthrombosis.J Thromb Haemost,2004,2:1305-1310.
    [59]Medina P,Navarro S,Estelles A,etal.Contribution of polymorphi-smsin theendothelial protein C receptor gene to soluble endotheli-al proteinC receptor andcirculating activated protein C levels, and thromboticrisk.Thromb Heamost,2004,91:905-911.
    [60]Kurosawa S,Stearns-Kurosawa DJ,Hidari N,et al.Identification offunctionalendothelial protein C receptor in human plasma.J ClinInvest.1997;100:411418.
    [61]Kurosawa S,Stearns-Kurosawa DJ,Carson CW,et al.Plasma levelsof endothelial cell protein C receptor are elevated in patients with sepsisand systemic lupus erythematosus:lack of correlation withthrombomodulin suggests involvement of different pathologicalprocesses.Blood.1998;91:725-727.
    [62]肖玲,冯涛,祝鸿雁,等.急性脑梗死患者血清IL-1与MMP-9的关系及意义[J].黑龙江医药,2011,24:210.
    [63]黄惠敏,王涛.炎证、动脉粥样硬化与缺血性卒中[J].国际脑血管病杂志,2007,15(6):464-468.
    [64]NaghavMi,LibbyP,Falk E,etal.Fromvulnerableplaque to vulnerablepatient-A call for new definitions and risk assessment strategies:Part[J].Circulation,2003,108:1664-1672.
    [65]LoweGDO The relationship between infaction,inflammation andcardiovascular diseases:an overview[J].AnnPeriodontol,2001,6(1):1-8.
    [66]ChoA,ReidyMA Matrixmetalloproteinase-9isnecessary for theregulation of smooth musclecellreplication andmigration after arterialinjury[J].CircRes,2002,91:845-851.
    [67]LindseyM,Wedin K,BrownMD,et al.Matrix2dependent mechanism ofneutrophilm ediated releasean dactivation of matrixme tall oprotei-nase9in myocardial ischemia reperfusion [J]Circulation,2001,103:2181-2187.
    [68]NewbyAC,Zaltsman AB.Molecularmechanisms in intimalhyper plasi-a[J].Pathol,2000,190(3):300-309.
    [69]DolleryCM,McEwan JR,HenneyAM.Matrixmetalloproteinases andcard iov ascular disease[J]CircRes,1995,77(5):863-868.
    [1]Touzani0,Boutin H,ChuquetJ,eta1.Potential mechanisms ofinterleukin—l involvement in cerebral ischaemia.J Neuroi mmunol,1999,100:203—215.
    [2]Zheng GZ,MichaelC。AntonG.Cerebral vessels express interleukin—lβafter focal cerebral ischemia[J].Brain Research,1998,784;210—217.
    [3]狄政莉,万琪,来华安,等.IL-1β和IL-6在脑缺血再灌注微血管内皮细胞炎证反应中的作用[J].西安医科大学学报,2001,22(5):432-434.
    [4]Ding Y,Young CN,LiJ,et a1.Reduced inflammatory mediator Express-ion by pre-reperfusion infusion into ischemic Territory in rats:areal-time polymerase chain reaction analysis.Neuroscience Letters,2003Dec26,353(3);173-176.
    [5]杜柏岩,关秀茹,高光强,等.IL-1β对大鼠脑缺血再灌注损伤的意义[J].哈尔滨医科大学学报,2000,34(2);124-125.
    [6]Lehxm annE.et a1.M icroglia and macrophages are major sources oflocally proced transforming growth factor-betal after transient middlecerebral artery occlusion in rats.G1ia,1998,24(4);437-438.
    [7]刘士民,郭玉璞.大鼠局灶脑缺血/再灌注模型TGT-β的表达[J].基础医学与临床,2000,20(1):70-73.
    [8]王社军,蒋传路,康军,等.大鼠脑缺血/再灌注后血脑屏障通透性的改变及转移生长因子的表达[J].中华神经外科杂志,2003,19(1):51-54.
    [9]Wang XK,Yue T,White TF,et a1.Transforming growth factor beta-1exhibits delayed gene expression following focal cerebralischemia.Brain Res Bull,1995,36(6):607—609.
    [10]ClarkWM,LautenJD,Lessor N,eta1.TimeCourse ofICAM-l Expressio-n and leukocyte subset infiItration in rat forehrain ischemia.Mol Chemneurophathol,1995,26;213.
    [11]KacimiR.KarlinerJS,KoudssiF,eta1.Expression and regulationOf adhesion molecules in Cardiac cells by cytokines response toacute hypoxia[J].Circ Res,1998,82(5);576-586.
    [12]ixon GL,Heyderman RS,van der LeyP,eta1.High-level endothelial Fselectin(CD62E) cell adhesion molecule expression by alipopolysa-ccharide deficient strain of Neisseria Meningitidis despite pooractivation of NF-kappaB transcription factor[J].Clin Exp Immunol,2004,135(1);85-93.
    [13]Argenbright LW,Barton RW.Interactions of leukocyte integrins withintercellular adhesion molecule1in theProduction of inflamma-tory vascular injury in vivo.The Shwartzmanreaction revisited[J]. ClinInvest,1992,89(1);259-272.
    [14]崔尧元,余勇,张晓彪,等.细胞间粘附分子1、肿瘤坏死因子α转录水平在缺血再灌注大鼠脑皮质中表达的相关性[J].中华实验外科杂志,1999,16(5):442-443.
    [15]葛海良,Wen Ye,Guo-Yuan Yang,A.等.小鼠局灶性脑缺血模型中细胞问粘附分子-l表达升高[J].中国神经免疫学和神经病学杂志,1999,6(3);147—152.
    [16]Esmon CT.Inflammation and thrombosis.J Thromb Haemost.2003;1:1343-1348.
    [17]Yamamoto K,Shimokawa T,Kojima T,et al.Regulation of murineprotein C gene expression in vivo:effects of tumor necrosis factor2a,inteleukin-l, and transforming growth faotor-β. Thromb Haemost,l999,82:l297-1301.
    [18]Gandrille S,Borgel D,Ireland H,et al.Protein S deficiency:a databaseof mutations.For the Plasma Coagulation Inhibitors Subcommittee ofthe Scientific and Standardization Committee of the InternationalSociety on Thrombosis and Haemostasis.Thromb Haemost,1997,77(6):1201-1214.
    [19]Fukudome K, Esmon CT. Identification, cloning, and regulation of anovel endothelial cell protein C/activated protein C receptor. J BiolChem,1994,269(42):26486-26491.
    [20]Fukudome K,Kurosawa S,Stearns Kurosawa DJ,et al.Theendothelia-l cell protein C receptor.Cell surface expression and directligan-d binding by the soluble receptor.J BiolChem,1996,271(29):17491-17498.
    [21]Kurosawa S,Stearns-Kurosawa DJ,Hidari N, et al.Identification offunctional endothelial protein C receptor in human plasma.J ClinInvest.1997;100:411-418.
    [22]Kurosawa S,Stearns-Kurosawa DJ,Carson CW,et al.Plasma levelsof endothelial cell protein C receptor are elevated in patients with sepsisand systemic lupus erythematosus:lack of correlation withthrombomodulin suggests involvement of different pathologicalprocesses.Blood.1998;91:725-727.
    [23] Regan LM,Stearns-Kurosawa DJ,Kurosawa S,et al.The endothelialcell protein C receptor.Inhibition of activated protein C anticoagulantfunction without modulation of reaction with proteinase inhibitors.J BiolChem.1996;271:1749917503.
    [24]Liaw PC,Neuenschwander PF,Smirnov MD,et al.Mechanisms bywhich soluble endothelial cell protein C receptor modulates protein Cand activated protein C function.J Biol Chem.2000;275:54475452.
    [25]LiDQ,LokeshwarBL,SclomonA,etal.Regulation of MMP-9Produetio-n by human comeal epithelial cells.ExpEye Res,2001,73(4):449-459.
    [26]BrauerPR.MMPs-role in cardiovaseular develoPment and disease.Front Biosci,200611:447-478.
    [27]IwataM,Pillai M,RamakrishnanA,etal.Reduced exPression ofinducible gelatinaseB/matrix metalloproteinase-9in monoeytes fromPatients with myelodysPlastie syndrome:eorrelation of indueible levelswith the Percentage of cytogenetieally marked cells And with marrowcellularity.Blood,2007,109:85-92.
    [28]ZhangRL,ChoppM,Zaloga C,et a1.The temporal profiles of ICAM-1protein and Mrna expression after transient MCA occlusion in therat.Brain Res,1995,682:182.
    [29]Yang GY,GongC,QinZ,eta1.Inhibition of TNF-a attenuate infarctvolume and ICAM-1expression in ischemic mouse brain.NeuroReport,1998.9:2131.
    [30]YangGY,MaoY,ZhouLF,eta1.Attenuation of temporary Focal cerebr-al ischemic injury in the mouse following Transfection with IL-1receptor antagonist.Brain Res Mol Brain Res,1999,72;129.
    [31]DeGraba WJ.The role of inflanmation after acute stroke:utility ofpursuinganti-adhesion molecule therany.Neuroloey,1998,51:862.
    [32]YangGY.Schielke GP,GongC,eta1.Expression of TNF-a andICAM-l after focal cerebral ischemiain IL-Ip converting enzyme deficientMice.J CerebBlood Flow Metab,1999,19:1109.
    [33]SchroeterM,KuryP,JanderS.Inflammatory gene expression Infoca-l cortical brain ischemia:differences between rats and mice. BrainResMol BrainRes,2003Sep10,117(1);1-7.
    [34]易兴阳,袁光固,周东,等.脑梗死患者周围血细胞因子研究[J].中风与神经疾病杂志,1996,13(6):333-335
    [35]易兴阳,潘继豹,池丽芬,等.进展性缺血性脑卒中患者细胞因子及黏附分子的研究[J].中国神经免疫学和神经病学杂志,2006,13(3);169-172.
    [36]禹爱梅,邹玉安.急性脑梗死患者血清中IL-1β及IL-6水平变化的研究[J].河北北方学院学报,2006,23(2):38-39.
    [37]王建茹,冯忠军,李娜,等.急性脑梗死患者血IL-1、IL-6、TNF、TM水平的变化及临床意义[J].中国免疫学杂志,2004,20(6);431-432.
    [38]Robert MF,ValeriaG,Hideaki H,eta1.Expression of a dominantNegative of interleukirrlp converting enzyme in transgeniC Miceprevents neuronal cell death induced by tropic factor withdrawal andischemic brain injury[J].EXP Med,1997,185:933-940.
    [39]Robert MF,ValeriaG,Hideaki H,eta1.Expression of a dominantNegative of interleukirrlp converting enzyme in transgeniC Miceprevents neuronal cell death induced by tropic factor withdrawal andischemic brain injury[J].EXP Med,1997,185:940~947.
    [40].Krupinski J,Kumar P,Kumar S,et a1.Increased expression ofTGF-beta1in Brain tissue after ischemic stroke inhumans[J].Stroke,1996,27(5);852-857.
    [41]王钢,黄建群.脑卒中患者转化生长因子与细胞粘附因子检测及分析[J].中华内科杂志,2000,39(5):309—311.
    [42]顾天华,龚艳春,王德治,等.高血压合并腔隙性脑梗死转移生长因子βl的变化[J].上海第二医科大学学报,2002,22(6);515—517.
    [43]程利萍,贾建民,濮孟久.IL-1β、TNF-a、TGF-βl与缺血性脑损害相关性研究[J].中国神经免疫学和神经病学杂志,2004,ll(1);36-38
    [44]何志义,欧阳巅,张强,等.老年急性脑血管病患者细胞因子及其受体的研究[J].中华老年心脑血管病杂志,2001,3(5);322-325.
    [45]郭正良,傅毅,辛晓瑜,等.急性脑梗死患者ox-LDL、TGF-βl和VCAM-1的检测[J].上海交通大学学报(医学版),2006,26(11);1274-1276.
    [46]Kawamata T,Ren J,Chan TC.Intracisternal osteogenic Protein-1enhances functional recovery folowing foca stoke.Neuroreport,1998,9(7):1441-1445.
    [47]CastellaJlos M,Castillo J,Garcia,eta1.Inflanmation mediateddamage in progressing lacunar infarct-tions[J].Stroke,2002,33;982-987.
    [48]De Matthaeis A,Greco A,Serviddio G,et al.Endothelial dysfuncti-onevaluated by flow mediated dilation is strongly Associated tometabolic syndrome in the elderly[J].Aging Clin Exp Res.2010,22(4):303-307.
    [49]Georges Bellon,Laurent Martiny,Arnaud Robint.Matrix metallopr-oteinases and matrikines in angiogenesis[J].Critical Reviews inOncology/Hematologr492004,49:203.
    [50]LoftusJ,NaylorR,goodallS,etal.Increasedmatrix metalloproteinase-9activity in unstable carotid plaques.A potential role in acuteplaque disruption[J].Stroke,2000,31:40.
    [51]Heo JH,Kim SH,Lee KY,etal.Increase in plasma matrixmetalloProteinase-9in acute stroke patients with thrombolysisfailure[J].Stroke,2003,34(6):e48.

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