未成熟心肌缺血再灌注损伤后L-精氨酸的保护作用

目的：用幼兔体内心脏缺血再灌注损伤模型，研究小剂量L-精氨酸对未成熟心肌的保护效果。方法：24只新西兰幼兔(3～4周龄)随机分4组，每组6只：正常对照组；缺血／再灌注组；L-精氨酸组；L-硝基精氨酸甲酯组。测定各组的心室血液动力学指标、血浆肌酸激酶和乳酸脱氢酶(lactate dehydrogenase，LDH)、心肌组织中总一氧化氮合酶(NOS)和诱导型一氧化氮合酶(iNOS)及eNOS(eNOS=总NOS-iNOS)活性。结果：L一精氨酸组左心室收缩压(LVSP)、心室内压力变化率(&;#177;dp／dt)、左心室舒张压(LVDt，)恢复明显高于缺血／再灌注组和L一硝基精氨酸甲酯组(P&;lt;0．05)；L-精氨酸组左心室舒张期末压(LVEDP)明显低于缺血／再灌注组和L-硝基精氨酸甲酯组(P&;lt;0．05)。L-精氨酸组的血浆肌酸激酶和LDH低于缺血／再灌注组和L-硝基精氨酸甲酯组(P&;lt;0．05)。缺血／再灌注组、L-精氨酸组、L-硝基精氨酸甲酯组总NOS高于正常对照组(P&;lt;0．05)；L-精氨酸组eNOS高于正常对照组、缺血／再灌注组、L-硝基精氨酸甲酯组(P&;lt;0.05)。4组iNOS差异无显著性意义(P&;gt;0．05)。结论：小剂量L-精氨酸能改善缺血／再灌注损伤后未成熟心肌的左心室血流动力学指标，这种保护作用是通过提高eNOS活性实现的，而与iNOS活性无关。     

果糖二磷酸镁对大鼠心肌缺血再灌注损伤的保护作用

目的：观察1，6二磷酸果糖和镁离子的合成药果糖二磷酸镁对心肌缺血再灌注损伤过程中血清中肌酸激酶，乳酸脱氢酶，Mg^2＋浓度，心肌组织内超氧化物歧化酶，丙二醛浓度的影响，并与单用1,6二磷酸果糖或硫酸镁相比较。 方法：实验于2004-10／2005-05在锦州医学院药理学实验室进行，取50只雄性SD大鼠随机分为5组，每组10只：①模型组：采用左冠状动脉下穿线，拉紧丝线引起心肌缺血，放松丝线给予再灌注的方法建立心肌缺血再灌注损伤动物模型，结扎冠脉左室前降支30min时经大鼠尾静脉注入生理盐水1mL，10min给药完毕，再灌注加min。②果糖二磷酸镁组：造模及给药时间和方法同模型组，注入药物为lmL果糖二磷酸镁（100mg／kg）。③1，6二磷酸果糖组：同前造模给药，药物为1mL 1,6二磷酸果糖（106mg／kg）。④硫酸镁组：同前造模给药，药物为硫酸镁（30mg／kg）。⑤假手术组：完成模型全部操作，只穿线不结扎。各组大鼠在再灌注40min后，均经颈动脉取血采用比色法测定肌酸激酶，乳酸脱氢酶活力及Mg^2＋浓度；于实验结束后立即取左室游离心肌组织0．5g，采用羟胺法测定超氧化物歧化酶活力，采用硫代巴比妥钠比色法测定丙二醛含量。 结果：50只大鼠进入结果分析。①血清中肌酸激酶活力：果糖二磷酸镁组、1,6二磷酸果糖组和硫酸镁组均低于模型组[（84．40&;#177;19．15），（86．90&;#177;5．68），（90．86&;#177;9．13），（105．43&;#177;3．95）μkat／L P〈0．051。②血清乳酸脱氢酶活力：果糖二磷酸镁组、1，6二磷酸果糖组和硫酸镁组均低于模型组[（47．57&;#177;19．58），（50．94&;#177;3．86），（50．45&;#177;5．37），（68．59&;#177;11．74）μkat／L,P〈0．011。③血清中Mg^2＋浓度：果糖二磷酸镁组和硫酸镁组均高于模型组[（0．92&;#177;0．06），（0．91&;#177;0．04），（0．75&;#177;0．03）mmol／L，P〈0．01]。④心肌组织超氧化物歧化酶活力：果糖二磷酸镁组和1，6二磷酸果糖组均高于模型组[（1．52&;#177;0．41），（1．44&;#177;0．39），（1．15&;#177;0．28）μkat／g，P〈0．051。⑤心肌组织内丙二醛含量：果糖二磷酸镁组和1,6二磷酸果糖组显著低于模型组[（17．08&;#177;23．12），（21．60&;#177;5．58），（50．13&;#177;18．21）nmol／g，P〈0．011。 结论：果糖二磷酸镁对缺血再灌注心肌损伤具有保护作用，很可能是通过1,6二磷酸果糖和硫酸镁协同作用而产生，其效果优于单用1，6二磷酸果糖或硫酸镁。其保护作用机制与增加血清中Mg^2＋浓度和组织内超氧化物歧化酶含量，减少血清中肌酸激酶，乳酸脱氢酶活力和组织内丙二醛含量及抗脂质过氧化有关。     

未成熟心肌缺血再灌注损伤后L-精氨酸的保护作用

目的:用幼兔体内心脏缺血再灌注损伤模型,研究小剂量L-精氨酸对未成熟心肌的保护效果。方法:24只新西兰幼兔(3～4周龄)随机分4组,每组6只:正常对照组;缺血/再灌注组;L-精氨酸组;L-硝基精氨酸甲酯组。测定各组的心室血液动力学指标、血浆肌酸激酶和乳酸脱氢酶(lactatedehydroge-nase,LDH)、心肌组织中总一氧化氮合酶(NOS)和诱导型一氧化氮合酶(iNOS)及eNOS(eNOS=总NOS-iNOS)活性。结果:L-精氨酸组左心室收缩压(LVSP)、心室内压力变化率(±dp/dt)、左心室舒张压(LVDP)恢复明显高于缺血/再灌注组和L-硝基精氨酸甲酯组(P<0.05);L-精氨酸组左心室舒张期末压(LVEDP)明显低于缺血/再灌注组和L-硝基精氨酸甲酯组(P<0.05)。L-精氨酸组的血浆肌酸激酶和LDH低于缺血/再灌注组和L-硝基精氨酸甲酯组(P<0.05)。缺血/再灌注组、L-精氨酸组、L-硝基精氨酸甲酯组总NOS高于正常对照组(P<0.05);L-精氨酸组eNOS高于正常对照组、缺血/再灌注组、L-硝基精氨酸甲酯组(P<0.05)。4组iNOS差异无显著性意义(P>0.05)。结论:小剂量L-精氨酸能改善缺血/再灌注损伤后未成熟心肌的左心室血流动力学指标,这种保护作用是通过提高eNOS活性实现的,而与iNOS活性无关。     

吗啡对大鼠心肌缺血/再灌注损伤的保护作用

缺血预处理(Ischemic preconditioning,IP),即反复短暂结扎冠状动脉可缩小随后长时间缺血导致的心肌梗死面积,是迄今最有力的心肌保护措施之一。但是．由于缺血时限、个体差异等问题使其在临床的应用受限,因而研究药理性预处理产生缺血预处理效应成为研究的新方向。有研究证实阿片肽     

氯化两面针碱对大鼠心肌缺血再灌注损伤的保护作用

背景：研究表明，自由基增多致脂质过氧化是缺血再灌注损伤的主要因素。性味苦辛平，有行气止痛、活血化瘀、祛风通络功用的芸香科植物两面针提取物有抗氧化作用。 目的：观察氯化两面针碱对大鼠心肌缺血再灌注损伤的作用，并分析其作用途径。 设计：随机对照实验。 单位：广西医科大学药理学教研室和化学教研室。 材料：选用健康Wistar大鼠60只，雌雄各半，体质量250～300g。氯化两面针碱（广西医科大学化学教研室提供，批号：20050609）。MS4000U生物信号定量记录分析系统（广州市龙飞达科技有限公司）。日立7170A型全自动生化分析仪。722N可见分光光度计（上海精密科学仪器有限公司）。盐酸维拉帕米（上海禾丰制药有限公司，批号：020701，2mL／支）。丙二醛、超氧化物歧化酶测定试剂盒（南京建成生物工程研究所产品）。 方法：实验于2004—06／2006—05在广西医科大学药理学教研室和化学教研室完成。①将心电图正常大鼠60只分性别按随机数字表法分为6组：假手术组，模型组，氯化两面针碱2，1，0．5mg／kg3个剂量组，阳性对照组，每组10只，雌雄各半。假手术组：穿线不结扎，90min后结束实验；其余50只大鼠：结扎冠状动脉左前降支缺血30min，再灌注60min。阳性对照组、不同剂量氯化两面针碱组、模型组：在结扎冠状动脉左前降支前10min经股静脉分别注射维拉帕米2mg／kg，氯化两面针碱2，1，0．5mg／kg，5mL／kg，等体积生理盐水。②再灌注的同时用标准肢体Ⅱ导联心电图连续监测，记录60min内各组心律失常类型、发生率及持续时间；并记录再灌注15min及60minST段的变化。③实验完毕，采用全自动生化分析仪检测血清心肌酶学指标。分别用硫代巴比妥酸法与黄嘌呤氧化酶法测定心肌组织丙二醛含量及超氧化物歧化酶活力。④两组间计量和计数资料差异比较采用t检验和X^2检验。 主要观察指标：各组大鼠心律失常发生情况、心电图ST段抬高程度、血清心肌酶学指标变化和心肌组织丙二醛含量、超氧化物歧化酶活力比较。 结果：大鼠60只均进入结果分析。①大鼠心律失常及心电图ST段抬高程度变化：1和2mg／kg氯化两面针碱组大鼠心律失常出现的时间明显迟于模型组（P〈0．05，0．01）。1和2mg／kg氯化两面针碱组和阳性对照组大鼠心律失常持续时间明显短于模型组（P〈0．05～0．01），各类型心律失常发生率明显少于模型组（P〈0．01），再灌注15和60min时ST段抬高程度均明显低于模型组（P〈0．05-0．01）。②血清心肌酶水平：模型组心肌缺血再灌注60min后明显高于假手术组（P〈0．01），1和2mg／kg氯化两面针碱组明显低于模型组（P〈0．01,P〈0．05），且随氯化两面针碱剂量增加，下降幅度增加。阳性对照组明显低于模型组（P〈0．05～0．01）。③心肌组织超氧化物歧化酶活力：模型组心肌缺血再灌注60min后明显低于假手术组（P〈0．01）；1和2mg／kg氯化两面针碱组明显高于模型组（P〈0．01），且随氯化两面针碱增加，上升幅度增加。④心肌组织丙二醛含量：模型组心肌缺血再灌注60min后明显高于假手术组（P〈0．01）。1和2mg／kg氯化两面针碱组明显低于模型组（P〈0．01），且随氯化两面针碱增加，下降幅度增加；阳性对照组明显低于模型组（P〈0．05）。 结论：①1和2mg／ks氯化两面针碱能降低心肌缺血再灌注大鼠心律失常的发生率，推迟心律失常的发生时间并缩短其持续时间，降低再灌注15和60min时ST段抬高程度；该作用效果与维拉帕米相当。②1和2mg／kg氯化两面针碱能减少心肌缺血再灌注大鼠心肌酶的释放，减轻氧自由基损伤程度，起到保护大鼠缺血再灌注心肌细胞损伤的作用，且该作用呈一定的剂量依赖性。     

银杏叶、硒对大鼠心肌缺血再灌注损伤的保护作用

目的 探讨微量元素硒和银杏叶对大鼠心肌缺血／再灌注损伤(IRI)的保护作用。方法 建立大鼠心肌缺血／再灌注模型，用硒和银杏叶溶液在模型建立前分别做预处理，观察尾动脉压、心律失常的变化，测定血液中LDH、SOD、GSH-PX和MDA的改变。结果 硒和银杏叶的预处理组，能降低血液中LDH和MDA含量，能提高SOD和GSH-PX活性，能升高血压和抗心律失常。结论 硒和银杏叶对大鼠心肌IRI具有一定的保护作用。     

妊娠期缺氧对子代大鼠成年后离体心肌缺血再灌注损伤的影响

目的：评价妊娠期缺氧对子代成年后心肌缺血再灌注损伤的作用。方法：在SD雌鼠妊娠期第15～21天给予氧浓度10．5％的低氧环境,建立妊娠期缺氧动物模型。缺氧组和对照组子代雄鼠同等条件下饲养至3个月龄作为实验用动物。建立离体鼠Langendorff模型,分别记录缺氧组和对照组模型平衡15rain后和缺血30min后再灌注1h内心脏机械功能变化和冠脉流量,测定再灌注1h冠脉流出液一氧化氮合酶（NOS）、内皮型一氧化氮合酶（eNOs）活性,计算梗死心肌占整个左心室质量的比例。结果：建立模型15min后,对照组和缺氧组的基础心脏机械功能和冠脉流量均无显著差异,但缺血再灌注后缺氧组心脏机械功能和冠脉流量的恢复均明显低于对照组。再灌注冠脉流出液中缺氧组NOS和eNOS活性均显著低于对照组。缺氧组心肌梗死面积明显大于对照组。结论：妊娠期缺氧可加重成年后离体心肌缺血再灌注损伤,其作用机制与eNOS活性下降有关。     

果糖二磷酸镁对大鼠心肌缺血再灌注损伤的保护作用

目的:观察1,6二磷酸果糖和镁离子的合成药果糖二磷酸镁对心肌缺血再灌注损伤过程中血清中肌酸激酶,乳酸脱氢酶,Mg2 浓度,心肌组织内超氧化物歧化酶,丙二醛浓度的影响,并与单用1,6二磷酸果糖或硫酸镁相比较。方法:实验于2004-10/2005-05在锦州医学院药理学实验室进行,取50只雄性SD大鼠随机分为5组,每组10只:①模型组:采用左冠状动脉下穿线,拉紧丝线引起心肌缺血,放松丝线给予再灌注的方法建立心肌缺血再灌注损伤动物模型,结扎冠脉左室前降支30min时经大鼠尾静脉注入生理盐水1mL,10min给药完毕,再灌注40min。②果糖二磷酸镁组:造模及给药时间和方法同模型组,注入药物为1mL果糖二磷酸镁(100mg/kg)。③1,6二磷酸果糖组:同前造模给药,药物为1mL1,6二磷酸果糖(106mg/kg)。④硫酸镁组:同前造模给药,药物为硫酸镁(30mg/kg)。⑤假手术组:完成模型全部操作,只穿线不结扎。各组大鼠在再灌注40min后,均经颈动脉取血采用比色法测定肌酸激酶,乳酸脱氢酶活力及Mg2 浓度;于实验结束后立即取左室游离心肌组织0.5g,采用羟胺法测定超氧化物歧化酶活力,采用硫代巴比妥钠比色法测定丙二醛含量。结果:50只大鼠进入结果分析。①血清中肌酸激酶活力:果糖二磷酸镁组、1,6二磷酸果糖组和硫酸镁组均低于模型组[(84.40±19.15),(86.90±5.68),(90.86±9.13),(105.43±3.95)μkat/L,P<0.05]。②血清乳酸脱氢酶活力:果糖二磷酸镁组、1,6二磷酸果糖组和硫酸镁组均低于模型组[(47.57±19.58),(50.94±3.86),(50.45±5.37),(68.59±11.74)μkat/L,P<0.01]。③血清中Mg2 浓度:果糖二磷酸镁组和硫酸镁组均高于模型组[(0.92±0.06),(0.91±0.04),(0.75±0.03)mmol/L,P<0.01]。④心肌组织超氧化物歧化酶活力:果糖二磷酸镁组和1,6二磷酸果糖组均高于模型组[(1.52±0.41),(1.44±0.39),(1.15±0.28)μkat/g,P<0.05]。⑤心肌组织内丙二醛含量:果糖二磷酸镁组和1,6二磷酸果糖组显著低于模型组[(17.08±23.12),(21.60±5.58),(50.13±18.21)nmol/g,P<0.01]。结论:果糖二磷酸镁对缺血再灌注心肌损伤具有保护作用,很可能是通过1,6二磷酸果糖和硫酸镁协同作用而产生,其效果优于单用1,6二磷酸果糖或硫酸镁。其保护作用机制与增加血清中Mg2 浓度和组织内超氧化物歧化酶含量,减少血清中肌酸激酶,乳酸脱氢酶活力和组织内丙二醛含量及抗脂质过氧化有关。     

氯化两面针碱对大鼠心肌缺血再灌注损伤的保护作用

背景:研究表明,自由基增多致脂质过氧化是缺血再灌注损伤的主要因素。性味苦辛平,有行气止痛、活血化瘀、祛风通络功用的芸香科植物两面针提取物有抗氧化作用。目的:观察氯化两面针碱对大鼠心肌缺血再灌注损伤的作用,并分析其作用途径。设计:随机对照实验。单位:广西医科大学药理学教研室和化学教研室。材料:选用健康Wistar大鼠60只,雌雄各半,体质量250～300g。氯化两面针碱(广西医科大学化学教研室提供,批号:20050609)。MS4000U生物信号定量记录分析系统(广州市龙飞达科技有限公司)。日立7170A型全自动生化分析仪。722N可见分光光度计(上海精密科学仪器有限公司)。盐酸维拉帕米(上海禾丰制药有限公司,批号:020701,2mL/支)。丙二醛、超氧化物歧化酶测定试剂盒(南京建成生物工程研究所产品)。方法:实验于2004-06/2006-05在广西医科大学药理学教研室和化学教研室完成。①将心电图正常大鼠60只分性别按随机数字表法分为6组:假手术组,模型组,氯化两面针碱2,1,0.5mg/kg3个剂量组,阳性对照组,每组10只,雌雄各半。假手术组:穿线不结扎,90min后结束实验;其余50只大鼠:结扎冠状动脉左前降支缺血30min,再灌注60min。阳性对照组、不同剂量氯化两面针碱组、模型组:在结扎冠状动脉左前降支前10min经股静脉分别注射维拉帕米2mg/kg,氯化两面针碱2,1,0.5mg/kg,5mL/kg,等体积生理盐水。②再灌注的同时用标准肢体Ⅱ导联心电图连续监测,记录60min内各组心律失常类型、发生率及持续时间;并记录再灌注15min及60minST段的变化。③实验完毕,采用全自动生化分析仪检测血清心肌酶学指标。分别用硫代巴比妥酸法与黄嘌呤氧化酶法测定心肌组织丙二醛含量及超氧化物歧化酶活力。④两组间计量和计数资料差异比较采用t检验和χ2检验。主要观察指标:各组大鼠心律失常发生情况、心电图ST段抬高程度、血清心肌酶学指标变化和心肌组织丙二醛含量、超氧化物歧化酶活力比较。结果:大鼠60只均进入结果分析。①大鼠心律失常及心电图ST段抬高程度变化:1和2mg/kg氯化两面针碱组大鼠心律失常出现的时间明显迟于模型组(P<0.05,0.01)。1和2mg/kg氯化两面针碱组和阳性对照组大鼠心律失常持续时间明显短于模型组(P<0.05～0.01),各类型心律失常发生率明显少于模型组(P<0.01),再灌注15和60min时ST段抬高程度均明显低于模型组(P<0.05～0.01)。②血清心肌酶水平:模型组心肌缺血再灌注60min后明显高于假手术组(P<0.01),1和2mg/kg氯化两面针碱组明显低于模型组(P<0.01,P<0.05),且随氯化两面针碱剂量增加,下降幅度增加。阳性对照组明显低于模型组(P<0.05～0.01)。③心肌组织超氧化物歧化酶活力:模型组心肌缺血再灌注60min后明显低于假手术组(P<0.01);1和2mg/kg氯化两面针碱组明显高于模型组(P<0.01),且随氯化两面针碱增加,上升幅度增加。④心肌组织丙二醛含量:模型组心肌缺血再灌注60min后明显高于假手术组(P<0.01)。1和2mg/kg氯化两面针碱组明显低于模型组(P<0.01),且随氯化两面针碱增加,下降幅度增加;阳性对照组明显低于模型组(P<0.05)。结论:①1和2mg/kg氯化两面针碱能降低心肌缺血再灌注大鼠心律失常的发生率,推迟心律失常的发生时间并缩短其持续时间,降低再灌注15和60min时ST段抬高程度;该作用效果与维拉帕米相当。②1和2mg/kg氯化两面针碱能减少心肌缺血再灌注大鼠心肌酶的释放,减轻氧自由基损伤程度,起到保护大鼠缺血再灌注心肌细胞损伤的作用,且该作用呈一定的剂量依赖性。     

大鼠心肌缺血再灌注损伤与红花黄素的保护作用

目的：观察大鼠心肌缺血再灌注损伤模型心肌组织中超氧化物歧化酶、谷胱甘肽过氧化物酶、诱导型一氧化氮合酶、总一氧化氮合酶活性及一氧化氮，丙二醛含量的变化，探讨红花黄素对离体大鼠缺血再灌注心肌的保护作用。 方法：①实验于2004—06／2005—02在南阳医学高等专科学校药理学教研室完成。选用健康Wistar大鼠32只，随机分为4组，每组8只：正常对照组、模型组、红花黄素组、地奥心血康组。②采用Langendofff创建的离体心脏灌流法建立离体大鼠心肌缺血缺氧再灌注损伤模型。以持续平衡的充有体积分数0．95O2＋0．05CO2混合气体的KH液进行非循环逆行灌流。灌注数秒后心脏恢复跳动。稳定15min后停灌30min，再灌40min，给药组在停灌前10min以红花黄素（0．33g生药／mL）或地奥心血康灌注，直至再灌后40min。正常对照组离体心脏持续灌注K—H液90min。模型组离体心脏灌注．K—H液35min，全心缺血25min，再灌注30min。③心肌中超氧化物歧化酶、谷胱甘肽过氧化物酶、一氧化氮合酶活性变化、一氧化氮、丙二醛含量测定按南京建成生物工程研究所提供的相应试剂盒说明完成。④分别进行成组t检验和配对t检验。 结果：进入结果分析大鼠32只。①超氧化物歧化酶、谷胱甘肽过氧化物酶活力：模型组明显低于其他3组（P〈0．05～0.01）；丙二醛含量：模型组明显高于其他3组（P〈0．05～0．01）。②一氧化氮含量：模型组明显低于其他3组（P〈0．05～0．01）。③诱导型一氧化氮合酶活力：地奥心血康组明显高于模型组（P〈0．01）；总一氧化氮合酶活力：模型组明显高于对照组和红花黄素组（P〈0．01），明显低于地奥心血康组（P〈0．05）。 结论：红花黄素对离体大鼠缺血再灌损伤的心肌具有保护作用，此作用可能与抑制心肌脂质过氧化、增强抗氧化能力有关。     

氯化镁对大鼠缺血再灌注损伤心肌的保护作用

目的:研究氯化镁对大鼠缺血再灌注损伤心肌是否具有保护性作用,同时探讨氯化镁的心肌保护作用机制。方法:实验于2004-06/07在锦州医学院药理学实验室完成,选用50只SD大鼠,采用整体大鼠急性心肌缺血再灌注损伤模型,用3个不同剂量的氯化镁给大鼠尾静脉注射,测定心肌组织中Ca2+和丙二醛含量以及血清中乳酸脱氢酶含量,并同时记录心电图监测心肌缺血再灌注时心律失常的发生情况率。结果:氯化镁可降低血清中乳酸脱氢酶含量,也能降低心肌组织中的丙二醛和Ca2+含量。氯化镁可减少心肌缺血再灌注损伤时室性心律失常发生率和缩短心律失常的持续时间。给药组再灌注时ST段抬高(mV)程度(其中氯化镁低、中、高剂量组分别为0.16±0.03,0.12±0.02,0.06±0.01)较缺血再灌注组(0.22±0.06)显著降低。结论:氯化镁对心肌再灌注损伤具有保护作用,其机制可能与缓解心肌细胞内钙超负荷和抑制脂质过氧化有关。     

Preconditionin effects of dexmedetomidine on myocardial ischemia/reperfusion injury in rats

Background: Preconditioning might protect the myocardium against ischemia/ reperfusion injury by reducing infarct size and preventing arrhythmias. Dexmedetomidine (DEX) is a highly selective α2-agonist used for sedoanalgesia in daily anesthetic practice. The cardioprotective effects of DEX on infarct size and on the incidence of arrhythmias observed after regional ischemia/reperfusion injury in vivo have not been reported.Objective: The aim of this study was to determine whether DEX exhibits a preconditioning effect and reduces infarct size and the incidence and duration of arrhythmias in a regional cardiac ischemia/reperfusion model in rats.Methods: Adult male Sprague-Dawley rats were anesthetized with sodium thiopental and mechanically ventilated (0.9 mL/100 g at 60 strokes/min) through a cannula inserted into the trachea after tracheotomy. Cardiac ischemia was then produced by ligating the left main coronary artery for 30 minutes, followed by a reperfusion period of 120 minutes. Blood pressure (BP) and heart rate (HR) were monitored and echocardiograms (ECGs) were performed. Arrhythmia was scored based on incidence and duration. The animals were randomly divided into 3 groups. The ischemic preconditioning (IPC) group underwent 5 minutes of ischemia followed by 5 minutes of reperfusion before the 30-minute ischemia/120-minute reperfusion period. In the DEX group, intraperitoneal (IP) DEX 1 mL (100 μg/kg) was administered 30 minutes before the ischemia/ reperfusion period. In the control group, IP saline 1 mL was administered 30 minutes before the ischemia/reperfusion period. After reperfusion, the heart was excised, demarcated with saline and ethanol to identify the occluded and nonoccluded myocardium, and cut into slices ~2 mm thick, that were then stained and placed between 2 glass plates. The risk zone and the infarct zone were compared between groups. The investigator assessing the infarcts was blinded to the study group.Results: Twenty-one adult (aged 4-6 months) male Sprague-Dawley rats weighing 280 to 360 g were included in the study; 7 rats were assigned to each group. BP, HR, and ECG readings were not significantly different between groups and did not change during the study. Arrythmias occurred during ischemia and reperfusion in all groups. The duration of the arrhythmias was significantly shorter and the arrhythmia score was significantly lower in the IPC group (all, P<0.05), compared with the control group; however, they were not significantly different in the DEX group. During the ischemic period, duration of ventricular tachycardia (VT) and ventricular premature contractions (VPC) in the DEX group was significantly longer than that observed in the IPC group (all, P<0.05). The duration of VPC was also significantly shorter than that observed in the control group (both, P<0.05). Duration of VT during the reperfusion period in the DEX group was significantly longer than that observed in both IPC and control groups (both, P<0.05). The mean (SD) percentage of damage was significantly lower in the IPC group (44.1% [2.0%]) and the DEX group (26.7% [2.0%]) compared with the control group (69.0% [3.0%]; both, P<0.05). The percentage of damage in the DEX group was also significantly lower compared with the IPC group (P<0.05).Conclusions: This small, experimental in vivo study found that DEX was associated with reduced infarct size in ischemia/reperfusion injury in regional ischemia in this rat model but had no effect on the incidence of arrhythmias. Future studies are needed to clarify these findings.     

葡萄糖酸镁对离体大鼠心肌缺血再灌注细胞凋亡的抑制效应

目的:观察葡萄糖酸镁对离体大鼠心肌缺血再灌注损伤心肌细胞凋亡的影响。方法:实验于2005-10/2006-01在辽宁医学院药理实验室完成。选用雄性SD大鼠48只,体质量250～300g,按随机排列表法将大鼠分为对照组、缺血再灌注组、葡萄糖酸镁组,每组16只,建立Langendorff离体大鼠心肌缺血再灌注损伤模型。(1)每组各取8只:①对照组:改良的K-H缓冲液持续灌流110min。K-H缓冲液成分(mmol/L)如下:NaCl118.1,NaHCO325.0,KH2PO41.2,MgSO40.6,CaCl22.0,KCl4.7,Glucose11.0。②缺血再灌注组:改良的K-H缓冲液持续灌注至各项指标稳定后,约20min,停灌30min,再灌60min。③葡萄糖酸镁组:灌注方法同缺血再灌注组,但将K-H缓冲液内加葡萄糖酸镁2.4mmol/L。取左室心肌标本测总超氧化物歧化酶活性,丙二醛、Ca2 含量。(2)每组其余8只:①对照组K-H缓冲液持续灌流170min。②缺血再灌注组和葡萄糖酸镁组持续灌注至各项指标稳定后停灌30min,再灌注120min。观察对细胞凋亡的影响。(3)组间计量资料差异比较采用单因素方差分析。结果:SD大鼠共48只均进入结果分析。①缺血再灌注组大鼠心肌组织中丙二醛、Ca2 含量较对照组明显升高(P<0.01),总超氧化物歧化酶活性较对照组明显降低(P<0.01)。②葡萄糖酸镁组与缺血再灌注组比较,总超氧化物歧化酶活性明显升高(P<0.01),丙二醛、Ca2 含量明显降低(P<0.01)。③缺血再灌注组细胞凋亡指数显著高于对照组(P<0.01)。④葡萄糖酸镁组细胞凋亡指数与缺血再灌注组比较显著降低(P<0.01)。结论:葡萄糖酸镁有抑制心肌缺血再灌注损伤中心肌细胞凋亡的作用。其机制可能与葡萄糖酸镁减轻钙超载、清除氧自由基、减少脂质过氧化有关。     

脂质载体前列腺素E1对大鼠心肌缺血-再灌注损伤的保护作用

目的探讨脂质载体前列腺素E1（liposomal prostaglandin E1，Lipo-PGE1）抗心肌缺血-再灌注损伤的可能机制。方法用结扎冠状动脉的方法制备在体心肌缺血-再灌注损伤模型，将大鼠随机分为3组：假手术组、模型组、Lipo-PGE1保护组。用酶联免疫和放射免疫法测定缺血-再灌注损伤后血妊娠相关血浆蛋白。A（PAPP—A）、肿瘤坏死因子-a（TNF-a）的含量；亚硝酸盐比色测定血清超氧化物歧化酶（SOD）活性，TBA荧光显色法测定脂质过氧化物（LPO）含量；发色底物显色法测定组织型纤溶酶原激活物（t-PA）及纤溶酶原激活物抑制剂（PAI-1）；计算心肌梗死范围。结果与模型组相比，Lipo-PGE1保护组梗死面积减小（P〈0．01），模型组PAPP-A、TNF—a浓度明显高于假手术组（P〈0．01），Lipo-PGE1组PAPP—A、TNF-a浓度明显低于模型组（P〈0．01）；血清LPO含量明显降低，SOD活性显著升高（P〈0．01）；Lipo-PGE1提高t—PA活性，降低PAI-1活性（P〈0．01）。结论Lipo-PGE1通过减少炎症因子的产生、增加SOD活力、降低LPO含量和提高纤溶功能而保护缺血-再灌注损伤的心肌。     

烟碱对心肌缺血/再灌注损伤大鼠炎症细胞因子的影响

目的 探讨烟碱对心肌缺血/再灌注(I/R)损伤大鼠炎症细胞因子的影响.方法 50只健康雄性SD大鼠按随机数字表法分为假手术组、I/R组、烟碱高剂量(400μg/kg)组、烟碱低剂量(40μg/kg)组及α-银环蛇毒素(α-BGT,1μg/kg)组5组,每组10只.采用结扎心脏左冠状动脉前降支30 min、再灌注90 min制作大鼠心肌I/R损伤模型;假手术组仅穿线不结扎.制模前30 min各药物组颈静脉注射相应剂量药物干预,假手术组和I/R组给予等量生理盐水.于再灌注末取右颈动脉血,测定肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、IL-10浓度和肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)活性;然后处死动物,取缺血区心肌组织测定髓过氧化物酶(MPO)活性;采用免疫组化和逆转录-聚合酶链反应检测心肌组织细胞间黏附分子-1(ICAM-1)蛋白及mRNA表达,并观察心肌超微结构.结果 与假手术组比较,I/R组血浆TNF-α、IL-8、IL-10、CK-MB、cTnI、心肌MPO活性及ICAM-1蛋白和mRNA表达均显著升高[TNF-α(ng/L):158.7±32.7比31.5±5.8,IL-8(ng/L):0.71±0.06比0.30±0.04,IL-10(ng/L):69.0±7.8比41.4±4.3,CK-MB(U/L):2 540±169比1 120±102,cTnI(μg/L):26.2±4.6比0.9±0.2,MPO(U/g):4.2±0.6比1.6±0.4,ICAM-1蛋白:0.210±0.025比0.100±0.018,ICAM-1 mRNA:1.82±0.23比1.18±0.20,P＜0.05或P＜0.01],病理学显示心肌组织损伤较重.与I/R组比较,烟碱高剂量组血浆TNF-α、IL-8降低[TNF-α(67.3±9.8)ng/L,IL-8(0.47±0.04)ng/L],IL-10升高[(147.5±12.5)ng/L],CK-MB、cTnI及心肌MPO活性、ICAM-1蛋白和mRNA均降低[CK-MB(1 282±145)U/L,cTnI(4.7±1.4)μg/L,MPO(2.5±0.4)U/g,ICAM-1蛋白0.140±0.026,ICAM-1 mRNA 1.31±0.25,P＜0.05或P＜0.01],心肌组织损伤减轻;而烟碱低剂量组和α-BGT组上述指标与I/R组比较差异无统计学意义.结论 烟碱可阻断内皮细胞表达黏附分子,阻断中性粒细胞黏附、游出,改善抗炎/促炎反应平衡,从而拮抗大鼠心肌I/R损伤时的过度炎症反应.     

Cardioprotective effects of ozone oxidative preconditioning in an in vivo model of ischemia/reperfusion injury in rats

Abstract

Background. Several studies have demonstrated the beneficial effects of ozone oxidative preconditioning in several pathologies characterized by cellular oxidative and inflammatory burden. The present study was designed to investigate the cardioprotective effects of oxidative preconditioning in ischemia/reperfusion (I/R) injury. Methods. Rats were randomly assigned into five groups. Groups 1 and 2 were normal and I/R groups, respectively. Two of the other groups received two different doses of ozone therapies by rectal insufflations. The last group received vehicle (oxygen). Rats were subjected to myocardial I/R (40min/10min). Heart rate and ventricular arrhythmias were recorded during I/R progress. At the end of reperfusion, plasma creatine kinase-MB (CK-MB) activity and total nitrate/nitrite (NO_x) were determined. In addition, lactate, adenine nucleotides, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and myeloperoxidase (MPO) activity were estimated in the heart left ventricle. Histological examination was also performed to visualize the protective cellular effects. Results. Both doses of ozone therapy were equally protective in reducing CK-MB release. However, the higher dose was more effective in reducing oxidative stress, lactate accumulation, elevated MPO activity and plasma NO_x as well as preserving myocardial adenine nucleotides. Histological examination also revealed better improvement with a higher dose of ozone therapy compared to the I/R group. Conclusion. Ozone therapy can afford significant cardioprotection against biochemical and histological changes associated with I/R injury.     

Cardioprotective effects of acidified sodium nitrite in myocardial ischemia with reperfusion

The effects of acidified sodium nitrite (NaNO2) which releases nitric oxide, a substance which is thought to be indistinguishable from endothelium-derived relaxing factor, were investigated in a 6-h model of myocardial ischemia (MI) with reperfusion in open-chest, anesthetized cats. Acidified NaNO2 (12.5-50 mmol/kg/hr) was infused i.v., starting 30 min postocclusion followed by reperfusion 1 hr later, in cats subjected to MI by occlusion of the left anterior descending coronary artery. Acidified NaNO2 infusion (25 and 50 mmol/kg/hr) resulted in significantly lower plasma creatine kinase activities at every time beyond 1 hr for the MI + vehicle group, and was not significantly different when compared to sham MI + NaNO2 controls. The areas at risk expressed as percentage of the total left ventricular weights were not significantly different between the MI + vehicle and MI + acidified NaNO2 groups. However, the necrotic area expressed as a percentage of the myocardial area at risk was significantly lower in the 25 and 50 mmol/kg/hr NaNO2-treated cats. Cardiac myeloperoxidase activities indicated that significantly fewer neutrophils were attracted to the ischemic zone of the NaNO2-treated MI cats when compared to the vehicle-infused MI cats. Acidified NaNO2 significantly inhibited platelet aggregation in a dose-dependent manner in cat platelet-rich plasma. Thus, acidified NaNO2 exerts a significant protective action during ischemia and reperfusion injury, which suggests that endothelium-derived relaxing factor has a cardioprotective effect in MI.     

Cardioprotective effects of ozone oxidative preconditioning in an in vivo model of ischemia/reperfusion injury in rats

Abstract Background. Several studies have demonstrated the beneficial effects of ozone oxidative preconditioning in several pathologies characterized by cellular oxidative and inflammatory burden. The present study was designed to investigate the cardioprotective effects of oxidative preconditioning in ischemia/reperfusion (I/R) injury. Methods. Rats were randomly assigned into five groups. Groups 1 and 2 were normal and I/R groups, respectively. Two of the other groups received two different doses of ozone therapies by rectal insufflations. The last group received vehicle (oxygen). Rats were subjected to myocardial I/R (40min/10min). Heart rate and ventricular arrhythmias were recorded during I/R progress. At the end of reperfusion, plasma creatine kinase-MB (CK-MB) activity and total nitrate/nitrite (NO(x)) were determined. In addition, lactate, adenine nucleotides, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and myeloperoxidase (MPO) activity were estimated in the heart left ventricle. Histological examination was also performed to visualize the protective cellular effects. Results. Both doses of ozone therapy were equally protective in reducing CK-MB release. However, the higher dose was more effective in reducing oxidative stress, lactate accumulation, elevated MPO activity and plasma NO(x) as well as preserving myocardial adenine nucleotides. Histological examination also revealed better improvement with a higher dose of ozone therapy compared to the I/R group. Conclusion. Ozone therapy can afford significant cardioprotection against biochemical and histological changes associated with I/R injury.     

Cardioprotective effects of authentic nitric oxide in myocardial ischemia with reperfusion.

BACKGROUND AND METHODS: The purpose of this study was to determine the effects of nitric oxide (NO), believed to be endothelium-derived relaxing factor on reperfusion injury after myocardial ischemia (MI). The effects of NO were investigated in a 6-hr model of MI with reperfusion in open-chest, anesthetized cats. A solution containing NO was infused iv starting 30 min after occlusion of the left anterior descending coronary artery, continuing through reperfusion 1 hr later, and lasting for 5.5 hr. Estimated NO concentration in the circulation was 1 to 2 x 10(-9) M. RESULTS: The areas-at-risk expressed as a percentage of the total left ventricular weights were not significantly different among either of the MI groups. However, the necrotic area (expressed as a percentage of the myocardial area-at-risk) was significantly (p less than .01) lower in the NO-treated MI cats compared with the MI + vehicle group. Cardiac myeloperoxidase activities indicated that significantly (p less than .05) fewer neutrophils were attracted to the necrotic zone of the NO-treated MI cats when compared with MI cats receiving only the vehicle. Sodium nitrate (NaNO2) (pH 7.4), a major breakdown product of NO, failed to exert any protective effect in this same model of MI and reperfusion. CONCLUSIONS: NO appears to provide significant myocardial protection after ischemia and reperfusion. NO may afford cardioprotection by incorporation into circulating blood cells (i.e., neutrophils, platelets), thereby inhibiting their accumulation and adherence in the ischemic region, or by a direct cardiac cytoprotective effect. Further studies using NO donors rather than NO would be an appropriate clinically relevant mode of treatment in MI.     

L-精氨酸对糖尿病大鼠心肌缺血再灌注损伤的影响

目的:观察糖尿病大鼠心肌缺血再灌注时血管紧张素Ⅱ、胰岛素样生长因子1、醛固酮、细胞间黏附分子1和自由基代谢的变化及L-精氨酸对其的影响。方法:实验于2005-02/2006-06在江苏大学医学院机能学实验室完成。①实验分组:腹腔注射链脲佐菌素制作糖尿病大鼠模型,30只大鼠造模成功。按随机数字表法分为3组(n=10):心肌缺血再灌注组:开胸结扎冠脉,造成心肌缺血,60min后放松再灌注60min;L-精氨酸治疗组:于手术前4周灌胃L-精氨酸250mg/(kg·d),然后重复心肌缺血再灌注组操作;假手术组:完成操作后只穿线不结扎,观察2h作为对照。实验结束时心室取血6mL,摘取心脏,留取左心室心肌组织。②实验评估:检测大鼠血浆血管紧张素Ⅱ、醛固酮和血清胰岛素样生长因子1含量及心肌细胞间黏附分子1蛋白表达。检测大鼠血清、心肌组织超氧化物歧化酶、谷胱甘肽-过氧化物酶活性、丙二醛含量及心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性。结果:30只大鼠全部进入结果分析。①与假手术组相比,心肌缺血再灌注组血浆血管紧张素Ⅱ、醛固酮含量明显升高(P<0.05～0.01),血清胰岛素样生长因子1含量降低(P<0.05);L-精氨酸治疗4周后血浆血管紧张素Ⅱ、醛固酮含量低于心肌缺血再灌注组(P<0.05～0.01),血清胰岛素样生长因子1含量高于心肌缺血再灌注组(P<0.05)。②与假手术组相比,心肌缺血再灌注组血清、心肌丙二醛含量明显升高(P<0.05),血清、心肌超氧化物歧化酶和谷胱甘肽-过氧化物酶活性明显降低(P<0.05￣0.01);用L-精氨酸治疗4周后血清、心肌丙二醛含量低于心肌缺血再灌注组(P<0.05￣0.01),血清、心肌超氧化物歧化酶和谷胱甘肽-过氧化物酶活性高于心肌缺血再灌注组(P<0.05～0.01)。③与假手术组相比,心肌缺血再灌注组心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性明显降低(P<0.05),心肌细胞间黏附分子1蛋白表达明显升高(P<0.01);用L-精氨酸治疗4周后心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性明显高于心肌缺血再灌注组(P<0.05),心肌细胞间黏附分子1蛋白表达低于心肌缺血再灌注组(P<0.05)。结论:血管紧张素Ⅱ、醛固酮和胰岛素样生长因子1可能共同参与了糖尿病心肌缺血再灌注的发生,细胞间黏附分子1蛋白表达与糖尿病心肌损伤关系密切。L-精氨酸通过减少细胞间黏附分子1蛋白表达,起心肌保护作用。糖尿病心肌缺血再灌注时存在自由基代谢异常,补充L-精氨酸后,可通过提高超氧化物歧化酶、谷胱甘肽-过氧化物酶和ATP酶活性,降低丙二醛水平,减轻自由基损伤,改善心肌组织功能。