温阳益心活血化痰法对心肌缺血再灌注损伤NF-κB信号转导通路调控机制研究
|
摘要
近年来研究表明,心肌缺血再灌注损伤的主要机制之一是过度的炎症反应,在心肌缺血再灌注损伤的过程中炎性细胞因子大量释放并发挥重要的作用。而NF-κB信号转导通路参与介导细胞增殖、炎症、凋亡等多种生理过程,对于心肌缺血再灌注损伤的发生、发展具有关键作用。因此,本研究以心肌缺血再灌注损伤中炎症反应过程为研究主线,NF-κB信号转导通路为切入点,以温阳益心活血化痰法为干预手段,从细胞及分子生物学水平揭示温阳益心活血化痰法对心肌缺血再灌注损伤的抗炎效应及作用靶点,为优化治疗方案,提高临床疗效提供实验依据。
目的:探讨温阳益心活血化痰法对心肌缺血再灌注后NF-κB信号转导通路的干预作用,明确本法对心肌缺血再灌注炎症损伤的具体作用靶点,阐明其抗炎作用机理。
方法:通过结扎大鼠心脏左前降支动脉建立心肌缺血再灌注损伤动物模型,运用透射电镜观察心肌组织超微结构改变;全自动分析仪连续监测法检测大鼠血清LDH-L、CK水平;免疫印迹(western-blot)法检测心肌NIK、IKKβ、IκBα蛋白表达;采用逆转录-聚合酶链式反应(RT-PCR)及免疫组化法检测心肌NF-κBp65mRNA及蛋白表达;酶联免疫吸试验(ELISA)测定血清IL-1β、IL-6及IL-10的含量;利用免疫组化方法观察心肌TNF-α和ICAM-1蛋白表达。
结果:①温阳益心活血化痰法指导下创立的温心方可以显著改善心肌超微结构损伤,抑制LDH-L、CK的生成和释放,降低再灌注后心律失常发生率,对心肌缺血再灌注损伤有保护作用;②温心方能够抑制再灌注后心肌NIK、IKKβ表达,并同时上调IκBα蛋白表达,与模型组比较有显著性差异(P＜0.01);③温心方能明显抑制心肌NF-κBp65mRNA及蛋白表达,阻止其核移位,与模型组相比统计学有显著性差异(P＜0.01);④温心方能显著降低NF-κB调控的下游炎性细胞因子IL-1β、IL-6及TNF-α、ICAM-1的含量,并促进抑炎因子IL-10的表达,各项指标与模型组相比均有显著性差异(P＜0.01),且低剂量组明显优于高剂量组。
结论:温阳益心活血化痰法能够抑制血清心肌酶CK、LDH的生成和释放、降低再灌注后心律失常发生率、减轻心肌超微结构损伤,对心肌缺血再灌注损伤有保护作用。而其所具备良好的抗再灌注后炎症损伤作用,可能是通过抑制NF-κB信号转导通路上游激酶的活化,从而阻止NF-κB核移位,下调其转录调控的炎性因子表达,同时促进抑炎因子释放而实现的。
Recently,it has been reported that inflammatory response is one of the main mechanisms of myocardial ischemic reperfusion injury(MI/RI). A large amount of inflammatory cytokines are released and play an important role in the progression of MI/RI.NF-κB signal transduction pathway participates in vital physiological processes,such as cell proliferation、inflammation and apoptosis.Therefore,this research regards the inflammatory response of MI/RI as research main track and mainly focuses on NF-κB signal transduction pathway.The study used Wenxin compound as the intervening method to reveal anti-inflammatory effects and treatment target of warming yang and supplementingheart;promoting blood circulation and resolving phlegm(ab.as WSPR) on cellular and molecular level.Moreover,the research provides experimental evidence for optimizing treatment strategies and improving clinical effects.
Objective:To investigate the intervention effect of WSPR on NF-κB signal transduction pathway of MI/RI,showing the anti-inflammatory treatment target andmechanism of WSPR.
Method:MI/RI rat models were established by ligating the anterior branch of the left coronary artery and the myocardial ultrastructure at the ischemia region was observed under the transmission electron microscope.The content of CK and LDH in blood serum were measured with continuous monitoring using automatic blood chemistry analyzer.Besides, NIK、IKKβand IκBαprotein expression of myocardial tissues in rats were detected by western-blot;the gene and protein expression of NF-κBp65 were detected by immunohistochemistry and RT-PCR respectively.Moreover,the levels of serum IL-1β,IL-6 and IL-10 were measured by ELISA,and TNF-α, ICAM-1 expressions in myocardium were determined with immunohistochemistry.
Results:①Wenxin compound could significantly improve myocardial ultrastructural changes and inhibit the release of LDH-L and CK,decrease the incidence rate of reperfusion arrhythmias;②Wenxin compound was able to inhibit the protein expression of NIK,IKKβand enhanced the expression of IKBα,the difference is significant compared to the model group(P＜0.01);③Compared with model group,the gene and protein expression and the nuclear translocation of NF-κBp65 in the Wenxin compound were obviously inhibited(P＜0.01);④Wenxin compound could significantly decrease the contents of NF-κB downstream inflammatory factors such as IL-1β、IL-6 and TNF-α,ICAM-1(P＜0.01) and simultaneously strengthen the expression of IL-10.The differences of all the indicators were significant comparing to the model group(P＜0.01) and the effect of low dose is superior to high dose.
Conclusion:WSPR has cardioprotective effects against MI/RI in rats possibly by inhibiting the expression of Ck and LDH,and reducing arrhythmia and the injury of the myocardial ultrastructure.WSPR could protect myocardium from inflammatory damage during MI/RI,its mechanism might restrain the activation of upstream kinase of NF-κB signal transduction pathway and then inhibiting nuclear translocation of NF-κB,inhibiting the release of the inflammatory factors and promoting the expression of anti-inflammatory cytokines.
目的:探讨温阳益心活血化痰法对心肌缺血再灌注后NF-κB信号转导通路的干预作用,明确本法对心肌缺血再灌注炎症损伤的具体作用靶点,阐明其抗炎作用机理。
方法:通过结扎大鼠心脏左前降支动脉建立心肌缺血再灌注损伤动物模型,运用透射电镜观察心肌组织超微结构改变;全自动分析仪连续监测法检测大鼠血清LDH-L、CK水平;免疫印迹(western-blot)法检测心肌NIK、IKKβ、IκBα蛋白表达;采用逆转录-聚合酶链式反应(RT-PCR)及免疫组化法检测心肌NF-κBp65mRNA及蛋白表达;酶联免疫吸试验(ELISA)测定血清IL-1β、IL-6及IL-10的含量;利用免疫组化方法观察心肌TNF-α和ICAM-1蛋白表达。
结果:①温阳益心活血化痰法指导下创立的温心方可以显著改善心肌超微结构损伤,抑制LDH-L、CK的生成和释放,降低再灌注后心律失常发生率,对心肌缺血再灌注损伤有保护作用;②温心方能够抑制再灌注后心肌NIK、IKKβ表达,并同时上调IκBα蛋白表达,与模型组比较有显著性差异(P＜0.01);③温心方能明显抑制心肌NF-κBp65mRNA及蛋白表达,阻止其核移位,与模型组相比统计学有显著性差异(P＜0.01);④温心方能显著降低NF-κB调控的下游炎性细胞因子IL-1β、IL-6及TNF-α、ICAM-1的含量,并促进抑炎因子IL-10的表达,各项指标与模型组相比均有显著性差异(P＜0.01),且低剂量组明显优于高剂量组。
结论:温阳益心活血化痰法能够抑制血清心肌酶CK、LDH的生成和释放、降低再灌注后心律失常发生率、减轻心肌超微结构损伤,对心肌缺血再灌注损伤有保护作用。而其所具备良好的抗再灌注后炎症损伤作用,可能是通过抑制NF-κB信号转导通路上游激酶的活化,从而阻止NF-κB核移位,下调其转录调控的炎性因子表达,同时促进抑炎因子释放而实现的。
Recently,it has been reported that inflammatory response is one of the main mechanisms of myocardial ischemic reperfusion injury(MI/RI). A large amount of inflammatory cytokines are released and play an important role in the progression of MI/RI.NF-κB signal transduction pathway participates in vital physiological processes,such as cell proliferation、inflammation and apoptosis.Therefore,this research regards the inflammatory response of MI/RI as research main track and mainly focuses on NF-κB signal transduction pathway.The study used Wenxin compound as the intervening method to reveal anti-inflammatory effects and treatment target of warming yang and supplementingheart;promoting blood circulation and resolving phlegm(ab.as WSPR) on cellular and molecular level.Moreover,the research provides experimental evidence for optimizing treatment strategies and improving clinical effects.
Objective:To investigate the intervention effect of WSPR on NF-κB signal transduction pathway of MI/RI,showing the anti-inflammatory treatment target andmechanism of WSPR.
Method:MI/RI rat models were established by ligating the anterior branch of the left coronary artery and the myocardial ultrastructure at the ischemia region was observed under the transmission electron microscope.The content of CK and LDH in blood serum were measured with continuous monitoring using automatic blood chemistry analyzer.Besides, NIK、IKKβand IκBαprotein expression of myocardial tissues in rats were detected by western-blot;the gene and protein expression of NF-κBp65 were detected by immunohistochemistry and RT-PCR respectively.Moreover,the levels of serum IL-1β,IL-6 and IL-10 were measured by ELISA,and TNF-α, ICAM-1 expressions in myocardium were determined with immunohistochemistry.
Results:①Wenxin compound could significantly improve myocardial ultrastructural changes and inhibit the release of LDH-L and CK,decrease the incidence rate of reperfusion arrhythmias;②Wenxin compound was able to inhibit the protein expression of NIK,IKKβand enhanced the expression of IKBα,the difference is significant compared to the model group(P＜0.01);③Compared with model group,the gene and protein expression and the nuclear translocation of NF-κBp65 in the Wenxin compound were obviously inhibited(P＜0.01);④Wenxin compound could significantly decrease the contents of NF-κB downstream inflammatory factors such as IL-1β、IL-6 and TNF-α,ICAM-1(P＜0.01) and simultaneously strengthen the expression of IL-10.The differences of all the indicators were significant comparing to the model group(P＜0.01) and the effect of low dose is superior to high dose.
Conclusion:WSPR has cardioprotective effects against MI/RI in rats possibly by inhibiting the expression of Ck and LDH,and reducing arrhythmia and the injury of the myocardial ultrastructure.WSPR could protect myocardium from inflammatory damage during MI/RI,its mechanism might restrain the activation of upstream kinase of NF-κB signal transduction pathway and then inhibiting nuclear translocation of NF-κB,inhibiting the release of the inflammatory factors and promoting the expression of anti-inflammatory cytokines.
引文
[1]Schudlze CJ,wang W,Kumri R,et al.Imbalance between tissue inhibitor of metalloproteina-4 and matirx metalloporetinases during actue myocardial correlation of myocardial ischemia-reperfusion injury.Circulation,2003,107(19):2487-2492.
[2]赵慧娟,龙明智.心肌缺血再灌注损伤机制的研究近况[J].中西医结合心脑血管病杂志,2005,3(3):240-242.
[3]王保和.心肌缺血再灌注损伤机制研究及中药治疗进展[J].天津中医学院学报,2004,23(2):104-106.
[4]Hill GE:The inflammatory response to cardiopulmonary bypass[J].Int Anesthesiol Clin,1996,34:95-108.
[5]RossR.Cell biology of atherosclerosis[J].AnnRevPhysiol,1995,57:791-795.
[6]Maseri A.Inflammation,atherosclerosis,and ischemic events-exploring the hidden side of the moon[J].N Engl Med,1997,336(14):1014-1016.
[7]鹿小燕,张文高,周苏宁,等.人参及其皂甙抗心肌缺血再灌注损伤的研究进展.中国中医药信息杂志,2000,7(11):18-19.
[8]Griselli M,Herbert J,Hutchinson WL,et al.C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction[J].J Exp Med,1999,190(12):1733-1740.
[9]谭江宁,韩玲.心肌缺血-再灌注过程中的炎症反应.心血管病学进展,2004 z1:62-66.
[10]刘镇,连俊兰.心肌缺血再灌注炎症损伤机制的研究进展[J].中国心血管病研究杂志,2004,2(11):909-912.
[11]徐皓亮.细胞因子、趋化细胞因子与脑缺血后炎症损伤[J].中国药理学通报,1999,15(3):208-211.
[12]林艳君,张兰.异丙酚与缺血再灌注损伤炎症细胞因子表达的研究进展[J].四川医学,2007,28(1):24-26.
[13]Irwin M W,Mak S,Mann D L,et al.Tissue expression and immunolocali zation of tumor necrosis facto-alpha in postinfarction dysfunctional myocardium.Circulation,1999,99(11):1492.
[14]汪朝晖,廖玉华.如何评价心血管病中的炎症因子与炎症标志物[J].临床心血管病杂志,2007,23(1):1-2.
[15]陈少伯,王东琦.几种常见炎症标志物与冠心病关系的研究进展[J].实用医学杂志,2002,18(10):1123-1124.
[16]Wang ND,Pis J,Valencia R.Distribution of C-reacitve protein and its relation to risk factors,and coronary heart disease risk estimation in the Naitnnal Health and Nutrlon Examinstion Sutvey(NHANES)Ⅲ[J].Prev Cardiol.2001,4(3):109-114.
[17]Carcia-Moll X,Zouridakis E,Cole D,et al.C-reactive protein in patients with chronic stable angina:differences in baseline serum concetration between women and men[J].Eur Heart J,2000,21(19):1598-1606.
[18]余强,马根山.急性冠状动脉综合征与炎性相关的生化标志物研究进展[J].医学综述,2007,13(5):389-391.
[19]胡文兰,乔树宾.急性冠状动脉综合征与炎症标志物[J].中国心血管杂志,2007,12(3):220-223.
[20]李倩,蒋更如.炎症标志物在动脉粥样硬化性脑血管病中的应用[J].放射免疫学杂志,2005,18(3):217-219.
[21]杨平,杭永伦,温先勇,等.冠心病患者炎症标志物检测的临床意义[J].医学理论与实践,2007,20(1):9-10.
[22]成士清,刘成玉.炎症标志物CRP、IL-6和ICAM-1与冠心病的关系[J].齐鲁医学杂志,2006.21(2):180-182.
[23]O' MALLEY,LUDLAMC A,RIEMERMSA R A,et al.Early increase inlevels of soluble intercellular adhesion molecule-1(sICAM-1):potential risk factor for the acute coronary syndromes[J].Eur Heart J,2001,22(14):1226.
[24]Lefer AM,Campbell B,Shin YK,et al.Simvastatin preserves the ischemic reperfused myocardium in normocholesterolemic rat hearts[J].Circulation,1999,100(2):178.
[25]郭磊,吴延庆,曹原,等.氟伐他汀对兔心肌梗死再灌注血清白细胞介素-8及梗死面积的影响[J].临床心血管病杂志,2006,22(4):212-214.
[26]Scalia R,Gooszen ME,Jones SP,et al.Simvastatin exerts both anti inflammatory and cardioprotective effects in apolipoprotein E deficient mice [J].Circulation,2001,103(21):2598.
[27]Tiefenbacher CP,Kapitza J,Dietaz V,et al.Reduction of myocardial infarct size by fluvastatin.Am J Physiol Heart Circ Physiol,2003,285(1):59.
[28]李燕,马建群.他汀类药物与心肌缺血再灌注损伤[J].滨州医学院学报,2007,30(3):204-206.
[29]黄兵,左明章.细胞粘附分子与心肌缺血再灌注损伤[J].国外医学(生理、病理科学与临床分册),2001,21(3):195-197.
[30]刘英,程翔,廖玉华.钙通道阻滞剂与心血管免疫炎症的关系[J].中国药理学通报2007,23(2):141-143.
[31]张乐之,何华美.粉防己碱的抗炎作用与炎症白细胞cAMP的关系[J].中国药理学通 报,2003,19(7):75-80.
[32]Diaz A,Dickenson A H.Blockade of spinal N-and P-type,but not L-type,calcium channels inhibits the excitability of rat dorsal horn neurons produced by subcutaneous formalin inflammation[J].Pain,1997,69(1):93-100.
[33]唐惠芳,全智华.血管紧张素转换酶抑制剂与心肌缺血再灌注损伤[J].中国动脉硬化杂志,2002,10(3):271-273.
[34]张玉玲,周淑娴,雷娟,等.心肌梗死大鼠血管内皮功能及心功能变化与培哚普利的干预效应[J].中国组织工程研究与临床康复,2007,11(19):3752-3755.
[35]Lefer AM,Campbell B,Scalia R,et al.Synergism between platelets and neutrophils in provoking cardiac dysfunction after ischemia and reperfusion:role of selectins[J].Circulation,1998;98(13):1322-1328.
[36]赵莲,薛爽,陈芳,等.炎症、动脉粥样硬化和心脑血管疾病[J].心血管病学进展,2005,26(2):193-196.
[37]焦向英,罗宁,支建明,等.血小板激活因子及其拮抗剂银杏内酯B对大鼠心肌缺血再灌注损伤的影响[J].中国药理学与毒理学杂志,2002,16(2):81-87.
[38]王虹蛟,孟威宏,王强,等.抑肽酶的研究进展[J].中国实验诊断学,2008,12(7):941-947
[39]Pruefer D,Makowski J,Dahm M,et al.Aprotinin inhibits leukocyte-endothelial cell interactions after hemorrhage and reperfusion[J].Ann Thorac Surg,2003,75:210-216.
[40]张成伟,彭碧波,李继良,等.抑肽酶抑制体外循环及心肌缺血再灌注过程中炎性因子ET-1、IL-8的释放[J].武警医学,2002,13(4):202-204.
[41]Chen JW,Lin FY,Chen YH,et al.Carvedilol inhibits tumor necrosis factor-{alpha}-induced endothelial transcription factor activation,adhesion molecule expression,and adhesiveness to human mononuclear cells [J].Arterioscler rhromb Vasc Biol,2004,24:2075-2081.
[42]沈晓咏,肖明第.卡维地洛对心肌缺血再灌注损伤的保护作用研究进展[J].老年医学与保健,2007,13(4):254-256.
[43]Giomarelli P,Scolleta S,Borrelli E,et al.Myocardial and lung injury after cardiopulmonary bypass:role of interleukin(IL)-10[J].Ann Thorac Surg,2003,76(1):117-123.
[44]赵献明,李浪.急性心肌梗死心肌损伤的免疫学机制研究进展基[J].临床荟萃,2007,22(3):221-223.
[45]Tiefenbacher CP,Kapitza J,Dietz V et al.Reduction of m yocardial in farct size by fluvastation[J].Am J Physiol Heart Circ Physiol,2003,285(1):H59-64.
[46]孟阳,敖定椿,金钟兴,等.左旋精氨酸/一氧化氮在鼠心移植心肌缺血再灌注损伤中的研究[J].大连医科大学学报,2000,22(3):168-170.
[47]Le Deist F,Menasche P Kucharski C,et al.Hypothermia during cardiopulmonary bypass delays but does not prevent neutrophil-endothelial cell adhesion:a clinical study[J].Circulation,1995,92(Suppl):354-358.
[48]Paparella D,A Radi OO,Osman O,et al.The efects of high-dose heparin on inflammatory and coagulation parameters following cardiopulmonary bypass [J].Blood Coagul Fibrinolysis,2005,16(5):323-328.
[49]冯津萍,卢奕,赵炳让,等.黄芪对心肌缺血-再灌注时细胞因子变化的影响[J].天津医药,2002,30(8):454-456.
[50]陈志群,郭梅煌,马建芳.黄芪注射液对冠心病病人C反应蛋白和体液免疫的影响[J].实用中西医结合临床,2001,(1):3-4.
[51]呼敏凤,尚立芝,韦大文.川芎嗪预处理对心肌缺血再灌注损伤大鼠保护作用的实验研究[J].上海中医药杂志,2008,42(4):66-68.
[52]唐旭东,姜建青,赁常文,等.三七总皂昔对心肌缺血-再灌注中中性粒细胞浸润的影响及其核转录机制的实验研究[J].成都中医药大学学报,2002,25(3):32-35.
[53]顾国嵘,黄培志,费国强.三七总皂甙预处理对肿瘤坏死因子表达的影响[J].中国临床医学,2005,12(4):721-723.
[54]李梦妮,董文斌.丹参在缺血/再灌注损伤中的保护作用机制[J].中国急救医学,2005,25(5):351.
[55]黄政德,李鑫辉,谢雪姣,等.活血化瘀药对血瘀证心肌缺血再灌注损伤家兔内源性活性因子及炎症因子的影响[J].中华中医药学刊,2007,25(7):1319-1321.
[56]殷惠军,王显刚,史大卓.蒺藜总皂苷对大鼠缺血再灌注损伤心肌ICAM-1表达及中性粒细胞浸润的影响[J].解放军医学杂志,2006,31(6):534-535.
[57]曹维娟,何靖康.姜黄素对缺氧再给氧大鼠心脏微血管内皮细胞ICAM-1表达的影响[J].中国血液流变学杂志,2002,12(4):295-297.
[58]吴素焕,李利平,徐月清,等.血府逐瘀汤对家兔心肌缺血再灌注损伤的保护机制[J].中国临床康复,2006,10(3):63-65.
[59]朱陵群,赵明镜,王硕仁,等.血府逐瘀口服液对大鼠缺氧-再给氧损伤心脏微血管内皮细胞黏附分子表达的影响[J].中西医结合心脑血管病杂志,2006,4(8):692-694.
[60]倪军,张三林,卫世强,等.莪红注射液对不稳定心绞痛病人血小板颗粒膜蛋白、C反应蛋白的影响[J].中西医结合心脑血管杂志,2003,1(6):326-327.
[61]倪军,王军,张三林,等.莪红注射液对大鼠心肌缺血再灌注保护作用的研究[J].中西医结合心脑血管杂志,2003,1(10):586-587.
[62]黄烨,王宗仁,解娟,等.芪丹通脉片对心肌缺血/再灌注大鼠白细胞介素-10的影响[J]. 中国中医药信息杂志,2008,15(4):38-40.
[63]黎沛环,王宗仁,李军昌,等.芪丹通脉片对大鼠心肌缺血再灌注损伤时促炎细胞因子的影响[J].陕西医学杂志,2007,36(6):645-659.
[64]肖铁卉,王宗仁,李晶华,等.芪丹通脉片对实验性异丙肾上腺素致心肌损害的心肌ICAM-1表达影响[J].第四军医大学学报,2003,24(5):412-414.
[65]辛玲,李建英,王永.通心络胶囊治疗不稳定心绞痛临床观察[J].实用心脑肺血管病杂志,2008,16(4):256-259.
[66]张建伟,杨大成.通心络对急性心肌梗死急诊PCI患者再灌注损伤的保护性研究[J].医药产业资讯,2006,3(21):8-10.
[67]孔强,杨新春,刘秀兰,等.通心络对大鼠心肌梗死后心肌炎症反应及肿瘤坏死因子-α表达的影响[J].中国中西医结合杂志,2006,26(6):545-549.
[68]韩笑,刘建勋,马晓斌,等.双参通冠方对急性心肌缺血再灌注损伤时TNF-α,ICAM-1的影响[J].中国中药杂志,2004,29(11):1073-1075.
[69]王怡,王少峡,姜志浩.首乌丹参方预处理对大鼠心肌缺血再灌注损伤iNOS mRNA表达的影响[J].辽宁中医杂志,2007,34(12):1811-1814.
[70]王怡,王少峡,任明,等.首乌丹参方预处理对IR大鼠心肌梗死范围及血中TNF IL-I β的影响[J].四川中医,2007,25(1):7-9.
[71]陈竞纬,何燕,林钟香,等.益气养阴方对急性心肌缺血再灌注小鼠P-selectin的影响[J].陕西中医,2006,27(7):886-887.
[72]杨明军.芳香化浊方对大鼠心肌缺血-再灌注损伤保护作用的实验研究[J].中国中医药信息杂志,2003,10(8):12-13.
[73]ChuA J.Role of tissue factor in thrombosis.Coagulation-inflammation-thrombosis circuit[J].Front Biosci,2006,11:256-271.
[1]黄文林,朱孝峰.信号转导[M].北京:人民卫生出版,2005:1.
[2]刘胜中,杨双强.心肌缺血/再灌注损伤与细胞信号转导[J].心脏杂志,2008,20(2):223-225.
[3]马景德,齐秀芬.MAPKs信号通路及其与疾病关联性的研究现状[J].临床军医杂志,2004,32(2):95-97.
[4]Cain BS,Meldrum DR,Meng X,et al.p38 MAPK inhibition decreases TNF-a production and enhances postischemic human myocardial function[J].J SurgRes,1999,83(1):7-12.
[5]Weinbrenner C,Liu GS,Cohen MV,et al.Pboshorylation of tyrosine 182 of 183miogen-activated protein kinase correlates with the protection of preconditioninng in the rabbit heart[J].J Cell Moleo Cardiol,1997,29:2383-2391.
[6]Maulik N,Yoshida T,Zu YL,et al.Ischemic preconditioning triggers tyrosine kinase signaling:a potential role for MAPKAP kinase2[J].Am J Physiol,1998,275:H1857-1864.
[7]沈诚,范士志,陈建明,等.JAK/STAT通路对缺血再灌注心肌NF-κ B和TNF-α表达的影响[J].中国现代医学杂志,2006,16(7):985-987.
[8]Klampfer L.Signal transducers and activators of transcription(STATs):Novel targets of cehmoperventive and chemotherapeutic drugs[J].Curr Cancer Drug Targets,2006,6(2):107-121.
[9]Shouda T,Hiraoka K,Komiya S,et al.Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells[J].Cancer Lett,2006,231(2):176-184.
[10]王高频,孙英贤.JAK/STAT信号转导通路与心肌缺血再灌注[J].中国心血管病研究,2008,6(1):73-76.
[11]Stephanou A,Brar BK,Scarabelli TM,et al.Ischemia-induced STAT-1 expression and activation play a cirtical role in cardiomyocyte apoptosis[J].J Biol Chem,2000,275(14):10002-10008.
[12]Omura t,Yoshiyama M,Ishikura F,et al.Myocardial ischemia activates the JAK-STAT pathway through angiotensin Ⅱsignal in in vivo myocardium of rats[J].J Mol Cell Cardiol,2001,33(2):307-316.
[13]Mascareno E,El-Shafei M,Maulik N,et al.JAK/STAT signaling is associated with cadriac dysfunction during ischemia and reperfusion[J].Cicrulation,2001,104(3):325-329.
[14]韩笑,刘建勋.心肌缺血再灌注损伤的细胞信号转导机制[J].中国药理学通报,2004,20(1):4-7.
[15]赵正航,臧伟进,于晓红.腺苷对模拟缺血再灌注豚鼠心室肌细胞动作电位的影响及其 离子机制[J].中国药理学通报,2003,19(3):274-278.
[16]InagakiK,Hahn H S,Dorn G W 2nd,et al.Additive protection Of the ischemic heart ex vivo by combined treatment with PKC δ inhibitor and PKC ε activator[J].Circulation,2003,108(7):869-875.
[17]陈隽鹏,洪丰,郑顺利.蛋白激酶C信号传导在心肌缺血预处理中的作用研究进展[J].广东医学,2006,27(12):1914-1915.
[18]李鑫辉,黄政德.中医药对心肌缺血再灌注损伤的NF-κ B信号转导调控作用研究进展[J].中西医结合心脑血管病杂志.2007,5(2):144-145.
[19]Chandrasekar B,Nelson JF,Colston JT,et al.Calorie restriction Attenuates inflammatory responses to myocardial ischemia-reperfusion injury[J].Am J Physiol Heart Circ Physiol,2001,280(5):2094-2102.
[20]Morishita R,Sugimoto T,Aoki M,et al.Invivo transfection of cis element "decoy"against nuclear factor-kappaB binding site prevents myocardial infarction[J].Nat Med,1997,3(8):894-899.
[21]汪永义,薛松.NF κ B与心肌缺血再灌注损伤的研究进展[J].国外医学·心血管疾病分册,2002,29(3):140-142.
[1]苏静怡,李澈,苏哲坦主编.心脏:从生理到临床[M].北京:北京医科大学、中国协和医科大学联合出版社,1999年1月第1版.
[2]张东,金艳.对心肌再灌注损伤的中医病机的探讨[J].内蒙古中医药,2003,22(5):1-2.
[3]王磊,郭力恒,颜芳,等.黄春林论治急性心肌梗死经验撷英[J].辽宁中医杂志,2007,34(5):554-556.
[4]连乐燊,陈汉锐,郑创华,等.瓜蒌薤白类方与心血管系统相关的研究概况[J].中医药学刊,2006,24(7):1345-1346.
[5]李玉先,刘晓东,朱照静.半夏药理作用的研究述要[J].辽宁中医学院学报,2004,6(6):459-460.
[6]梁日欣,黄璐琦,刘菊福.药对川芎和赤芍对高脂血症大鼠降脂、抗氧化及血管内皮功能的实验观察[J].中国实验方剂学杂志,2002,8(1):43-45.
[7]蒋凤荣,张旭,范俊,等.麦冬药理作用研究进展[J].中医药学刊,2006,24(2):236-237.
[8]郑凌云,周祖玉,陶大昌.黄连素对缺血再灌注心肌细胞损伤的保护作用[J].甘肃中医,2003,34(3):542-545.
[9]陈业农,周逸平,汪克明,等.急性心肌缺血再灌注损伤大鼠模型制备方法的改进与评价[J].中国中医急症,2008,17(3):359-363.
[10]杨简,杨俊,丁家望,等.大鼠心肌缺血-再灌注损伤模型的改良及实验观察[J].中国老年学杂志.2008,28(10):961-963.
[11]张林,姜俊梅.宽胸逐瘀汤对家兔心肌缺血再灌注损伤保护作用的实验研究[J].辽宁中医药大学学报,2008,10(8):155-157.
[12]李海英,赵娟,佟长青.代谢酶影响因素的研究进展[J].现代中西医结合杂志,2008,17(10):1618-1619.
[13]钱俊,张亚臣.再灌注心律失常的发生机制、类型与治疗[J].心血管病学进展,2008,29(4):567-569.
[14]李春杰,曹洪欣,余柏林.中药预处理对家兔心肌缺血再灌注损伤保护作用的实验研究[J].中医药学刊,2004,22(10):1872-1873.
[15]于涛,曹洪欣.胸痹(冠心病)证候演变规律的临床研究[J].中医药信息,2004,21(3):44-45.
[16]刘镇,连俊兰.心肌缺血再灌注炎症损伤机制的研究进展[J].中国心血管病研究杂志,2004,2(11):909-912.
[17]Takuma Hayashi and Denise Faustman,Essential Role of Human Leukocyte Antigen-encoded Proteasome Subunits in NF-κ B Activation and Prevention of Tumor Necrosis Factor-α-induced Apoptosis[J].J Biol Chem,2000,275(7):5238-5247.
[18]Yingqiu Li,Junru Hu,Randi Vita,Binggang Sun,Hiroki Tabata,and Amnon Altman,SPAK kinase is a substrate and targrt of PKC θ in T-cellreceptor-induced AP-1activation pathway[J].EMBOJ,2004 March 10:23(5):1112-1122.
[19]王勇,黄文华.I κ B激酶的激活及其在NF-κ B活化过程中的作用[J].生物化学与生物物理进展,2001,28(4):455-458.
[20]Woronicz J D,Gao X,Cao Z,et al.I κ B kinase-β:NF-κ B activation and complex formation with I κ B kinase-α and NIK[J].Science,1997,278(5339):866-869.
[21]曾祥君,王学锋,陈林,等.NF-κ B激活的信号传导机制研究进展[J].重庆医学.2001,30(4):369-370.
[22]Kyriakis JM,Avruch J.Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation[J].Physiol Rev,2001,81:807-869.
[23]Wong SCY,Fukuchi M,Melnyk P,et al.Induction of cyclooxygenase-2 and activation of nuclear factor-κ B in myocardium of patients with congestive heart failure[J].Circulation,1998,98:100-103.
[24]Baeuerle PA,Henkel T.Function and activation of NF-kappa Bin the immune system[J].Annu Rev Immunol,1994,12:141-179.
[25]Li C,Browder W,Kao R.Early activation of transcrip-tion factor NF-κ B during lachemia in perfused rat heart[J].Am J physical,1999,276:H543.
[26]张艳芳,杨延桐.白细胞介素-1,8,10与心肌缺血-再灌注损伤[J].新乡医学院学报,2006,23(2):210-212.
[27]司良毅,陈运贞.白介素-1与心肌缺血再灌注损伤.重庆医学,1999,28(6):464-466.
[28]吴付轩,丁文惠,李大元,等.炎症递质在兔心肌缺血再灌注损伤中的作用[J].临床心血管病杂志,2000,16(2):85-87.
[29]rangogiannis NG Mendoza HL,Lindsey ML,et al.IL-10 is induced in the reperfused myocardium and maybe modulate the reaction to injury[J].The Joural of Immunolog,2000,165:2798-2808.
[30]Yang Z,Zingarelli B,Szahro C.Crucial role of endogenous interleukin-10production in myocardial ischemia/reperfusion injury[J].Circulation,2001,101:1019-1026.
[31]殷惠军,王显刚,史大卓.蒺藜总皂苷对心肌缺血再灌注损伤炎症因子TNF-α、IL-1β释放的影响[J].解放军医学杂志,2006,31(10):986-987.
[32]李拥军.肿瘤坏死因子、缺血再灌注损伤和心肌细胞凋亡[J].中国循环杂志,2002,17(5):397.
[33]贾卫国,安振海.可溶性黏附因子-1[J].华西医学,1997,12(4):465-466.
[34]殷惠军,王显刚,史大卓.蒺藜总皂苷对大鼠缺血再灌注损伤心肌ICAM-1表达及中性粒细胞浸润的影响.解放军医学杂志,2006,31(6):534-535.
[35]黄兵,左明章.细胞粘附分子与心肌缺血再灌注损伤[J].国外医学(生理、病理科学与临床分册),2001,21(3):195-197.
[36]梁萍,孙雷,唐建武等.细胞间粘附分子1、血管粘附分子1和肿瘤坏死因子α在人动脉粥样硬化病灶中的表达及意义.中国动脉硬化杂志,2004,12(4):427-429.
[2]赵慧娟,龙明智.心肌缺血再灌注损伤机制的研究近况[J].中西医结合心脑血管病杂志,2005,3(3):240-242.
[3]王保和.心肌缺血再灌注损伤机制研究及中药治疗进展[J].天津中医学院学报,2004,23(2):104-106.
[4]Hill GE:The inflammatory response to cardiopulmonary bypass[J].Int Anesthesiol Clin,1996,34:95-108.
[5]RossR.Cell biology of atherosclerosis[J].AnnRevPhysiol,1995,57:791-795.
[6]Maseri A.Inflammation,atherosclerosis,and ischemic events-exploring the hidden side of the moon[J].N Engl Med,1997,336(14):1014-1016.
[7]鹿小燕,张文高,周苏宁,等.人参及其皂甙抗心肌缺血再灌注损伤的研究进展.中国中医药信息杂志,2000,7(11):18-19.
[8]Griselli M,Herbert J,Hutchinson WL,et al.C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction[J].J Exp Med,1999,190(12):1733-1740.
[9]谭江宁,韩玲.心肌缺血-再灌注过程中的炎症反应.心血管病学进展,2004 z1:62-66.
[10]刘镇,连俊兰.心肌缺血再灌注炎症损伤机制的研究进展[J].中国心血管病研究杂志,2004,2(11):909-912.
[11]徐皓亮.细胞因子、趋化细胞因子与脑缺血后炎症损伤[J].中国药理学通报,1999,15(3):208-211.
[12]林艳君,张兰.异丙酚与缺血再灌注损伤炎症细胞因子表达的研究进展[J].四川医学,2007,28(1):24-26.
[13]Irwin M W,Mak S,Mann D L,et al.Tissue expression and immunolocali zation of tumor necrosis facto-alpha in postinfarction dysfunctional myocardium.Circulation,1999,99(11):1492.
[14]汪朝晖,廖玉华.如何评价心血管病中的炎症因子与炎症标志物[J].临床心血管病杂志,2007,23(1):1-2.
[15]陈少伯,王东琦.几种常见炎症标志物与冠心病关系的研究进展[J].实用医学杂志,2002,18(10):1123-1124.
[16]Wang ND,Pis J,Valencia R.Distribution of C-reacitve protein and its relation to risk factors,and coronary heart disease risk estimation in the Naitnnal Health and Nutrlon Examinstion Sutvey(NHANES)Ⅲ[J].Prev Cardiol.2001,4(3):109-114.
[17]Carcia-Moll X,Zouridakis E,Cole D,et al.C-reactive protein in patients with chronic stable angina:differences in baseline serum concetration between women and men[J].Eur Heart J,2000,21(19):1598-1606.
[18]余强,马根山.急性冠状动脉综合征与炎性相关的生化标志物研究进展[J].医学综述,2007,13(5):389-391.
[19]胡文兰,乔树宾.急性冠状动脉综合征与炎症标志物[J].中国心血管杂志,2007,12(3):220-223.
[20]李倩,蒋更如.炎症标志物在动脉粥样硬化性脑血管病中的应用[J].放射免疫学杂志,2005,18(3):217-219.
[21]杨平,杭永伦,温先勇,等.冠心病患者炎症标志物检测的临床意义[J].医学理论与实践,2007,20(1):9-10.
[22]成士清,刘成玉.炎症标志物CRP、IL-6和ICAM-1与冠心病的关系[J].齐鲁医学杂志,2006.21(2):180-182.
[23]O' MALLEY,LUDLAMC A,RIEMERMSA R A,et al.Early increase inlevels of soluble intercellular adhesion molecule-1(sICAM-1):potential risk factor for the acute coronary syndromes[J].Eur Heart J,2001,22(14):1226.
[24]Lefer AM,Campbell B,Shin YK,et al.Simvastatin preserves the ischemic reperfused myocardium in normocholesterolemic rat hearts[J].Circulation,1999,100(2):178.
[25]郭磊,吴延庆,曹原,等.氟伐他汀对兔心肌梗死再灌注血清白细胞介素-8及梗死面积的影响[J].临床心血管病杂志,2006,22(4):212-214.
[26]Scalia R,Gooszen ME,Jones SP,et al.Simvastatin exerts both anti inflammatory and cardioprotective effects in apolipoprotein E deficient mice [J].Circulation,2001,103(21):2598.
[27]Tiefenbacher CP,Kapitza J,Dietaz V,et al.Reduction of myocardial infarct size by fluvastatin.Am J Physiol Heart Circ Physiol,2003,285(1):59.
[28]李燕,马建群.他汀类药物与心肌缺血再灌注损伤[J].滨州医学院学报,2007,30(3):204-206.
[29]黄兵,左明章.细胞粘附分子与心肌缺血再灌注损伤[J].国外医学(生理、病理科学与临床分册),2001,21(3):195-197.
[30]刘英,程翔,廖玉华.钙通道阻滞剂与心血管免疫炎症的关系[J].中国药理学通报2007,23(2):141-143.
[31]张乐之,何华美.粉防己碱的抗炎作用与炎症白细胞cAMP的关系[J].中国药理学通 报,2003,19(7):75-80.
[32]Diaz A,Dickenson A H.Blockade of spinal N-and P-type,but not L-type,calcium channels inhibits the excitability of rat dorsal horn neurons produced by subcutaneous formalin inflammation[J].Pain,1997,69(1):93-100.
[33]唐惠芳,全智华.血管紧张素转换酶抑制剂与心肌缺血再灌注损伤[J].中国动脉硬化杂志,2002,10(3):271-273.
[34]张玉玲,周淑娴,雷娟,等.心肌梗死大鼠血管内皮功能及心功能变化与培哚普利的干预效应[J].中国组织工程研究与临床康复,2007,11(19):3752-3755.
[35]Lefer AM,Campbell B,Scalia R,et al.Synergism between platelets and neutrophils in provoking cardiac dysfunction after ischemia and reperfusion:role of selectins[J].Circulation,1998;98(13):1322-1328.
[36]赵莲,薛爽,陈芳,等.炎症、动脉粥样硬化和心脑血管疾病[J].心血管病学进展,2005,26(2):193-196.
[37]焦向英,罗宁,支建明,等.血小板激活因子及其拮抗剂银杏内酯B对大鼠心肌缺血再灌注损伤的影响[J].中国药理学与毒理学杂志,2002,16(2):81-87.
[38]王虹蛟,孟威宏,王强,等.抑肽酶的研究进展[J].中国实验诊断学,2008,12(7):941-947
[39]Pruefer D,Makowski J,Dahm M,et al.Aprotinin inhibits leukocyte-endothelial cell interactions after hemorrhage and reperfusion[J].Ann Thorac Surg,2003,75:210-216.
[40]张成伟,彭碧波,李继良,等.抑肽酶抑制体外循环及心肌缺血再灌注过程中炎性因子ET-1、IL-8的释放[J].武警医学,2002,13(4):202-204.
[41]Chen JW,Lin FY,Chen YH,et al.Carvedilol inhibits tumor necrosis factor-{alpha}-induced endothelial transcription factor activation,adhesion molecule expression,and adhesiveness to human mononuclear cells [J].Arterioscler rhromb Vasc Biol,2004,24:2075-2081.
[42]沈晓咏,肖明第.卡维地洛对心肌缺血再灌注损伤的保护作用研究进展[J].老年医学与保健,2007,13(4):254-256.
[43]Giomarelli P,Scolleta S,Borrelli E,et al.Myocardial and lung injury after cardiopulmonary bypass:role of interleukin(IL)-10[J].Ann Thorac Surg,2003,76(1):117-123.
[44]赵献明,李浪.急性心肌梗死心肌损伤的免疫学机制研究进展基[J].临床荟萃,2007,22(3):221-223.
[45]Tiefenbacher CP,Kapitza J,Dietz V et al.Reduction of m yocardial in farct size by fluvastation[J].Am J Physiol Heart Circ Physiol,2003,285(1):H59-64.
[46]孟阳,敖定椿,金钟兴,等.左旋精氨酸/一氧化氮在鼠心移植心肌缺血再灌注损伤中的研究[J].大连医科大学学报,2000,22(3):168-170.
[47]Le Deist F,Menasche P Kucharski C,et al.Hypothermia during cardiopulmonary bypass delays but does not prevent neutrophil-endothelial cell adhesion:a clinical study[J].Circulation,1995,92(Suppl):354-358.
[48]Paparella D,A Radi OO,Osman O,et al.The efects of high-dose heparin on inflammatory and coagulation parameters following cardiopulmonary bypass [J].Blood Coagul Fibrinolysis,2005,16(5):323-328.
[49]冯津萍,卢奕,赵炳让,等.黄芪对心肌缺血-再灌注时细胞因子变化的影响[J].天津医药,2002,30(8):454-456.
[50]陈志群,郭梅煌,马建芳.黄芪注射液对冠心病病人C反应蛋白和体液免疫的影响[J].实用中西医结合临床,2001,(1):3-4.
[51]呼敏凤,尚立芝,韦大文.川芎嗪预处理对心肌缺血再灌注损伤大鼠保护作用的实验研究[J].上海中医药杂志,2008,42(4):66-68.
[52]唐旭东,姜建青,赁常文,等.三七总皂昔对心肌缺血-再灌注中中性粒细胞浸润的影响及其核转录机制的实验研究[J].成都中医药大学学报,2002,25(3):32-35.
[53]顾国嵘,黄培志,费国强.三七总皂甙预处理对肿瘤坏死因子表达的影响[J].中国临床医学,2005,12(4):721-723.
[54]李梦妮,董文斌.丹参在缺血/再灌注损伤中的保护作用机制[J].中国急救医学,2005,25(5):351.
[55]黄政德,李鑫辉,谢雪姣,等.活血化瘀药对血瘀证心肌缺血再灌注损伤家兔内源性活性因子及炎症因子的影响[J].中华中医药学刊,2007,25(7):1319-1321.
[56]殷惠军,王显刚,史大卓.蒺藜总皂苷对大鼠缺血再灌注损伤心肌ICAM-1表达及中性粒细胞浸润的影响[J].解放军医学杂志,2006,31(6):534-535.
[57]曹维娟,何靖康.姜黄素对缺氧再给氧大鼠心脏微血管内皮细胞ICAM-1表达的影响[J].中国血液流变学杂志,2002,12(4):295-297.
[58]吴素焕,李利平,徐月清,等.血府逐瘀汤对家兔心肌缺血再灌注损伤的保护机制[J].中国临床康复,2006,10(3):63-65.
[59]朱陵群,赵明镜,王硕仁,等.血府逐瘀口服液对大鼠缺氧-再给氧损伤心脏微血管内皮细胞黏附分子表达的影响[J].中西医结合心脑血管病杂志,2006,4(8):692-694.
[60]倪军,张三林,卫世强,等.莪红注射液对不稳定心绞痛病人血小板颗粒膜蛋白、C反应蛋白的影响[J].中西医结合心脑血管杂志,2003,1(6):326-327.
[61]倪军,王军,张三林,等.莪红注射液对大鼠心肌缺血再灌注保护作用的研究[J].中西医结合心脑血管杂志,2003,1(10):586-587.
[62]黄烨,王宗仁,解娟,等.芪丹通脉片对心肌缺血/再灌注大鼠白细胞介素-10的影响[J]. 中国中医药信息杂志,2008,15(4):38-40.
[63]黎沛环,王宗仁,李军昌,等.芪丹通脉片对大鼠心肌缺血再灌注损伤时促炎细胞因子的影响[J].陕西医学杂志,2007,36(6):645-659.
[64]肖铁卉,王宗仁,李晶华,等.芪丹通脉片对实验性异丙肾上腺素致心肌损害的心肌ICAM-1表达影响[J].第四军医大学学报,2003,24(5):412-414.
[65]辛玲,李建英,王永.通心络胶囊治疗不稳定心绞痛临床观察[J].实用心脑肺血管病杂志,2008,16(4):256-259.
[66]张建伟,杨大成.通心络对急性心肌梗死急诊PCI患者再灌注损伤的保护性研究[J].医药产业资讯,2006,3(21):8-10.
[67]孔强,杨新春,刘秀兰,等.通心络对大鼠心肌梗死后心肌炎症反应及肿瘤坏死因子-α表达的影响[J].中国中西医结合杂志,2006,26(6):545-549.
[68]韩笑,刘建勋,马晓斌,等.双参通冠方对急性心肌缺血再灌注损伤时TNF-α,ICAM-1的影响[J].中国中药杂志,2004,29(11):1073-1075.
[69]王怡,王少峡,姜志浩.首乌丹参方预处理对大鼠心肌缺血再灌注损伤iNOS mRNA表达的影响[J].辽宁中医杂志,2007,34(12):1811-1814.
[70]王怡,王少峡,任明,等.首乌丹参方预处理对IR大鼠心肌梗死范围及血中TNF IL-I β的影响[J].四川中医,2007,25(1):7-9.
[71]陈竞纬,何燕,林钟香,等.益气养阴方对急性心肌缺血再灌注小鼠P-selectin的影响[J].陕西中医,2006,27(7):886-887.
[72]杨明军.芳香化浊方对大鼠心肌缺血-再灌注损伤保护作用的实验研究[J].中国中医药信息杂志,2003,10(8):12-13.
[73]ChuA J.Role of tissue factor in thrombosis.Coagulation-inflammation-thrombosis circuit[J].Front Biosci,2006,11:256-271.
[1]黄文林,朱孝峰.信号转导[M].北京:人民卫生出版,2005:1.
[2]刘胜中,杨双强.心肌缺血/再灌注损伤与细胞信号转导[J].心脏杂志,2008,20(2):223-225.
[3]马景德,齐秀芬.MAPKs信号通路及其与疾病关联性的研究现状[J].临床军医杂志,2004,32(2):95-97.
[4]Cain BS,Meldrum DR,Meng X,et al.p38 MAPK inhibition decreases TNF-a production and enhances postischemic human myocardial function[J].J SurgRes,1999,83(1):7-12.
[5]Weinbrenner C,Liu GS,Cohen MV,et al.Pboshorylation of tyrosine 182 of 183miogen-activated protein kinase correlates with the protection of preconditioninng in the rabbit heart[J].J Cell Moleo Cardiol,1997,29:2383-2391.
[6]Maulik N,Yoshida T,Zu YL,et al.Ischemic preconditioning triggers tyrosine kinase signaling:a potential role for MAPKAP kinase2[J].Am J Physiol,1998,275:H1857-1864.
[7]沈诚,范士志,陈建明,等.JAK/STAT通路对缺血再灌注心肌NF-κ B和TNF-α表达的影响[J].中国现代医学杂志,2006,16(7):985-987.
[8]Klampfer L.Signal transducers and activators of transcription(STATs):Novel targets of cehmoperventive and chemotherapeutic drugs[J].Curr Cancer Drug Targets,2006,6(2):107-121.
[9]Shouda T,Hiraoka K,Komiya S,et al.Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells[J].Cancer Lett,2006,231(2):176-184.
[10]王高频,孙英贤.JAK/STAT信号转导通路与心肌缺血再灌注[J].中国心血管病研究,2008,6(1):73-76.
[11]Stephanou A,Brar BK,Scarabelli TM,et al.Ischemia-induced STAT-1 expression and activation play a cirtical role in cardiomyocyte apoptosis[J].J Biol Chem,2000,275(14):10002-10008.
[12]Omura t,Yoshiyama M,Ishikura F,et al.Myocardial ischemia activates the JAK-STAT pathway through angiotensin Ⅱsignal in in vivo myocardium of rats[J].J Mol Cell Cardiol,2001,33(2):307-316.
[13]Mascareno E,El-Shafei M,Maulik N,et al.JAK/STAT signaling is associated with cadriac dysfunction during ischemia and reperfusion[J].Cicrulation,2001,104(3):325-329.
[14]韩笑,刘建勋.心肌缺血再灌注损伤的细胞信号转导机制[J].中国药理学通报,2004,20(1):4-7.
[15]赵正航,臧伟进,于晓红.腺苷对模拟缺血再灌注豚鼠心室肌细胞动作电位的影响及其 离子机制[J].中国药理学通报,2003,19(3):274-278.
[16]InagakiK,Hahn H S,Dorn G W 2nd,et al.Additive protection Of the ischemic heart ex vivo by combined treatment with PKC δ inhibitor and PKC ε activator[J].Circulation,2003,108(7):869-875.
[17]陈隽鹏,洪丰,郑顺利.蛋白激酶C信号传导在心肌缺血预处理中的作用研究进展[J].广东医学,2006,27(12):1914-1915.
[18]李鑫辉,黄政德.中医药对心肌缺血再灌注损伤的NF-κ B信号转导调控作用研究进展[J].中西医结合心脑血管病杂志.2007,5(2):144-145.
[19]Chandrasekar B,Nelson JF,Colston JT,et al.Calorie restriction Attenuates inflammatory responses to myocardial ischemia-reperfusion injury[J].Am J Physiol Heart Circ Physiol,2001,280(5):2094-2102.
[20]Morishita R,Sugimoto T,Aoki M,et al.Invivo transfection of cis element "decoy"against nuclear factor-kappaB binding site prevents myocardial infarction[J].Nat Med,1997,3(8):894-899.
[21]汪永义,薛松.NF κ B与心肌缺血再灌注损伤的研究进展[J].国外医学·心血管疾病分册,2002,29(3):140-142.
[1]苏静怡,李澈,苏哲坦主编.心脏:从生理到临床[M].北京:北京医科大学、中国协和医科大学联合出版社,1999年1月第1版.
[2]张东,金艳.对心肌再灌注损伤的中医病机的探讨[J].内蒙古中医药,2003,22(5):1-2.
[3]王磊,郭力恒,颜芳,等.黄春林论治急性心肌梗死经验撷英[J].辽宁中医杂志,2007,34(5):554-556.
[4]连乐燊,陈汉锐,郑创华,等.瓜蒌薤白类方与心血管系统相关的研究概况[J].中医药学刊,2006,24(7):1345-1346.
[5]李玉先,刘晓东,朱照静.半夏药理作用的研究述要[J].辽宁中医学院学报,2004,6(6):459-460.
[6]梁日欣,黄璐琦,刘菊福.药对川芎和赤芍对高脂血症大鼠降脂、抗氧化及血管内皮功能的实验观察[J].中国实验方剂学杂志,2002,8(1):43-45.
[7]蒋凤荣,张旭,范俊,等.麦冬药理作用研究进展[J].中医药学刊,2006,24(2):236-237.
[8]郑凌云,周祖玉,陶大昌.黄连素对缺血再灌注心肌细胞损伤的保护作用[J].甘肃中医,2003,34(3):542-545.
[9]陈业农,周逸平,汪克明,等.急性心肌缺血再灌注损伤大鼠模型制备方法的改进与评价[J].中国中医急症,2008,17(3):359-363.
[10]杨简,杨俊,丁家望,等.大鼠心肌缺血-再灌注损伤模型的改良及实验观察[J].中国老年学杂志.2008,28(10):961-963.
[11]张林,姜俊梅.宽胸逐瘀汤对家兔心肌缺血再灌注损伤保护作用的实验研究[J].辽宁中医药大学学报,2008,10(8):155-157.
[12]李海英,赵娟,佟长青.代谢酶影响因素的研究进展[J].现代中西医结合杂志,2008,17(10):1618-1619.
[13]钱俊,张亚臣.再灌注心律失常的发生机制、类型与治疗[J].心血管病学进展,2008,29(4):567-569.
[14]李春杰,曹洪欣,余柏林.中药预处理对家兔心肌缺血再灌注损伤保护作用的实验研究[J].中医药学刊,2004,22(10):1872-1873.
[15]于涛,曹洪欣.胸痹(冠心病)证候演变规律的临床研究[J].中医药信息,2004,21(3):44-45.
[16]刘镇,连俊兰.心肌缺血再灌注炎症损伤机制的研究进展[J].中国心血管病研究杂志,2004,2(11):909-912.
[17]Takuma Hayashi and Denise Faustman,Essential Role of Human Leukocyte Antigen-encoded Proteasome Subunits in NF-κ B Activation and Prevention of Tumor Necrosis Factor-α-induced Apoptosis[J].J Biol Chem,2000,275(7):5238-5247.
[18]Yingqiu Li,Junru Hu,Randi Vita,Binggang Sun,Hiroki Tabata,and Amnon Altman,SPAK kinase is a substrate and targrt of PKC θ in T-cellreceptor-induced AP-1activation pathway[J].EMBOJ,2004 March 10:23(5):1112-1122.
[19]王勇,黄文华.I κ B激酶的激活及其在NF-κ B活化过程中的作用[J].生物化学与生物物理进展,2001,28(4):455-458.
[20]Woronicz J D,Gao X,Cao Z,et al.I κ B kinase-β:NF-κ B activation and complex formation with I κ B kinase-α and NIK[J].Science,1997,278(5339):866-869.
[21]曾祥君,王学锋,陈林,等.NF-κ B激活的信号传导机制研究进展[J].重庆医学.2001,30(4):369-370.
[22]Kyriakis JM,Avruch J.Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation[J].Physiol Rev,2001,81:807-869.
[23]Wong SCY,Fukuchi M,Melnyk P,et al.Induction of cyclooxygenase-2 and activation of nuclear factor-κ B in myocardium of patients with congestive heart failure[J].Circulation,1998,98:100-103.
[24]Baeuerle PA,Henkel T.Function and activation of NF-kappa Bin the immune system[J].Annu Rev Immunol,1994,12:141-179.
[25]Li C,Browder W,Kao R.Early activation of transcrip-tion factor NF-κ B during lachemia in perfused rat heart[J].Am J physical,1999,276:H543.
[26]张艳芳,杨延桐.白细胞介素-1,8,10与心肌缺血-再灌注损伤[J].新乡医学院学报,2006,23(2):210-212.
[27]司良毅,陈运贞.白介素-1与心肌缺血再灌注损伤.重庆医学,1999,28(6):464-466.
[28]吴付轩,丁文惠,李大元,等.炎症递质在兔心肌缺血再灌注损伤中的作用[J].临床心血管病杂志,2000,16(2):85-87.
[29]rangogiannis NG Mendoza HL,Lindsey ML,et al.IL-10 is induced in the reperfused myocardium and maybe modulate the reaction to injury[J].The Joural of Immunolog,2000,165:2798-2808.
[30]Yang Z,Zingarelli B,Szahro C.Crucial role of endogenous interleukin-10production in myocardial ischemia/reperfusion injury[J].Circulation,2001,101:1019-1026.
[31]殷惠军,王显刚,史大卓.蒺藜总皂苷对心肌缺血再灌注损伤炎症因子TNF-α、IL-1β释放的影响[J].解放军医学杂志,2006,31(10):986-987.
[32]李拥军.肿瘤坏死因子、缺血再灌注损伤和心肌细胞凋亡[J].中国循环杂志,2002,17(5):397.
[33]贾卫国,安振海.可溶性黏附因子-1[J].华西医学,1997,12(4):465-466.
[34]殷惠军,王显刚,史大卓.蒺藜总皂苷对大鼠缺血再灌注损伤心肌ICAM-1表达及中性粒细胞浸润的影响.解放军医学杂志,2006,31(6):534-535.
[35]黄兵,左明章.细胞粘附分子与心肌缺血再灌注损伤[J].国外医学(生理、病理科学与临床分册),2001,21(3):195-197.
[36]梁萍,孙雷,唐建武等.细胞间粘附分子1、血管粘附分子1和肿瘤坏死因子α在人动脉粥样硬化病灶中的表达及意义.中国动脉硬化杂志,2004,12(4):427-429.