3，6—（二甲氨基）—二苯并碘杂六环柠檬酸盐保护大鼠缺血再灌注心肌与抗脂质过氧化的关系

在大鼠在体心肌缺血再灌注模型上，观察了３、６（二甲氨基）二笨并碘杂六环柠檬酸盐（１６５）的抗心肌缺血再灌注损伤及抗脂质过氧化作用结果表明１－６５能明显改善缺血再灌注所致的心肌光镜及电镜下细胞结构损伤，升高心肌超氧化物歧化酶和谷胱甘肽过氧化物酶活性，减少丙二醛生成提示Ｉ６５对心肌缺血再灌注损伤的保护作用与保护氧自由基清除酶的活性．防止膜脂质过氧化有关     

3,6—（二甲氨基）—二苯并碘杂六环柠檬酸盐保护大鼠缺血…

在大鼠在体心肌缺血再灌注模型上，观察了３，６－（二甲氨基）－二苯并碘杂六环柠檬酸盐（Ｉ－６５）的抗心肌缺血再灌注损伤及抗脂质过氧化作用。结果表明Ｉ－６５能明显改善缺血再灌注所致的心肌光镜及电镜下细胞结构损伤，升高心肌超氧化物歧人酶和谷胱甘肽过氧化物酶活性，减少丙二醛生成，提示Ｉ－６５对心肌缺血再灌注损伤的保护作用与保护氧自由基清除酶的活性，防止膜脂质过氧化有关。     

心律平对缺血再灌注心脏保护作用的实验研究

目的 探讨心律平（抗心律失常药）对缺血再灌注心肌的保护效果.方法 大鼠24只,离体心脏灌注,随机分为试验组与对照组：2组均应用停跳液,心脏停跳后,停灌注120 min,再灌注30 min,实验组在停跳液中加入心律平.分别测定再灌注5,10,30 min时,左心室收缩功能（LVDPi）及冠脉流量（Vi）,检测冠脉流出液中CPK-MB、LDH、TnT量;再灌注30 min,取左心室前壁内膜,检查心肌超微结构变化.结果 再灌注5,10,30 min实验组左心肌收缩功能恢复均好于对照组;漏出液中CPK-MB、LDH、TnT含量均少于对照组组.实验组超微结构损害较对照组轻.结论 停跳液中加用心律平,可减少缺血再灌注损伤,有显著的心肌保护作用.     

羟苯氨酮保护大鼠心脏对抗心肌缺血-再灌注损伤

目的研究强心扩血管新药羟苯氨酮(oxyphenamone)对心肌缺血-再灌注损伤的保护作用。方法对离体或在体大鼠心脏，阻断冠脉前降支10 min后行再灌注15 min(离体)或30 min(在体)，形成心肌缺血-再灌注损伤模型，从心电图、心肌酶学与心肌超微结构等方面观察药效。结果羟苯氨酮(离体心脏灌流1-10 μmol·L^-1，或静脉注射0.1-1.0 mg·kg^-1)剂量依赖性地明显减少再灌注时的心律失常，对抗损伤所致心肌CPK，LDH与MDA的变化，减轻心肌超微结构损伤。结论羟苯氨酮明显保护离体和在体大鼠心肌对抗冠脉阻断所致缺血-再灌注损伤。     

维拉帕米抗缺血心肌脂质过氧化与促进前列环素合成作用

“钙拮抗剂维拉帕米对离体大鼠心脏缺氧再给氧损伤和在体大鼠心脏缺血再灌注损伤均有预防性保护作用。维拉帕米能显著减少缺血心肌磷酸肌酸激酶释放,降低丙二醛含量和保护超氧化物歧化酶活性。在整体动物心肌缺血再灌注损伤实验,维拉帕米能显著促进缺血心肌前列环素合成。结果表明维拉帕米对心肌缺血再灌注损伤的保护作用与抗脂质过氧化有关,其促进前列环素合成作用可能与其抗心肌缺血有关。     

地塞米松抗氧化作用及其对I/R大鼠心脏功能和超微结构的影响

目的 探讨地塞米松的抗氧化作用及其对缺血-再灌注(I/R)大鼠心脏功能和心肌超微结构的影响.方法 SD大鼠随机分成地塞米松组、对照组,分别予地塞米松和生理盐水预处理.24小时后构建Langendorff离体心脏I/R动物模型,缺血30 min后再灌注60 min,动态观测缺血前及再灌注期间心脏功能的改变;测定心肌丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化酶(GSH-Px)水平;观察心肌超微结构变化.结果 与对照组相比,地塞米松组MDA水平显著降低(P＜0.01),SOD、CAT、GSH-Px水平显著升高(P＜0.05);地塞米松可改善再灌注期间心脏功能(LVDP、±dp/dtmax、CF P＜0.01)及减轻缺血再灌注后心肌超微结构的损伤.结论 地塞米松升高I/R心肌组织抗氧自由基酶的水平,抑制脂质过氧化反应,对缺血再灌注大鼠的心脏具有延迟保护作用.     

1，6-二磷酸果糖对幼兔离体心脏的保护作用

目的 研究1,6-二磷酸果糖(FDP)对幼兔离体心脏缺血一再灌注损伤的影响。方法建立幼兔离体灌流左心室顺灌做功模型,行缺血一再灌注试验。于缺血期间多次施加含5mmol／LFDP的St．ThomasⅡ号停搏液,经过120分钟缺血、30分钟再灌注,观察心功能、冠脉液肌酸激酶(CK)含量和心肌超微结构的变化。结果FDP组的心功能恢复情况优于对照组,心肌CK漏出量显著低于对照组．心肌超微结构损伤比对照组显著减轻。结论FDP对幼兔离体心脏缺血一再灌注损伤有保护作用。     

碟脉灵注射液对心肌缺血再灌注大鼠脂质过氧化的影响

目的：观察碟脉灵注射液对大鼠心肌缺血再灌注损伤脂质过氧化的影响。方法：将雄性Wistar大鼠30只（250～300g），随机分为假手术组、再灌模型组、碟脉灵组，每组10只。在乙醚麻醉下制备在体大鼠心肌缺血再灌注模型，各组动物在冠脉结扎60min时，各组大鼠分别舌下静脉注射碟脉灵注射液或生理盐水5ml/kg，然后松解结扎线进行再灌注。再灌注120min后，分别取血及心脏测血清及心肌中丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性，并对大鼠心脏进行N—BT染色测心肌梗死面积（MIS）。结果：碟脉灵注射液能显低降缺血再灌注大鼠血清及心肌中MDA含量及升高血清及心肌中SOD活性（P〈0．05）；亦能显缩小缺血再灌注大鼠MIS（P〈0．05）。结论：碟脉灵注射液对缺血再灌注造成的心肌损伤具有明显的保护作用，可能与增强机体对自由基的清除能力，减少脂质过氧化产物的堆积有关。     

丹酚酸A对大鼠心肌缺血再灌注性损伤的保护作用

用Langendorff离体大鼠心脏缺血再灌注模型,研究了丹酚酸A(SalA)对心肌缺血再灌注性损伤的保护作用。结果显示,SalA可以降低由于心肌缺血再灌注引起的室颤发生率,减少乳酸脱氢酶(LDH)从胞体中的漏出,降低缺血心肌组织中脂质过氧化产物MDA的含量,从而证明SalA对离体大鼠心肌缺血再灌注性损伤具有一定的保护作用。     

二氢槲皮素预处理对心肌缺血/再灌注损伤抗氧化作用的影响

目的探讨二氢槲皮素(dihydroquercetin,DDQ)对大鼠离体心脏缺血/再灌注损伤抗氧化作用的影响。方法SD大鼠40只,随机分为正常组、模型组、二氢槲皮素低剂量组(5 mg·L~(-1))、二氢槲皮素高剂量组(10 mg·L~(-1))4组。使用Langendorff逆行恒压灌流方式建立离体大鼠心脏I/R模型。观察I/R期间DDQ对左心室舒张压、左心室收缩压、室内压最大上升速率、室内压最大下降速率和心率的影响。乳酸脱氢酶(LDH)水平和血清肌酸激酶(CK)的含量均采用酶联免疫吸附法进行分析,TTC染色法评价心肌梗死程度,测定心肌组织中超氧化物歧化酶(SOD)、还原型谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)和丙二醛(MDA)含量,HE染色观察心肌组织学结构的病变。结果与模型组比,DDQ预处理组能够明显改善血流动力学的各项指标;DDQ预处理组可使心肌组织中的SOD和GSH/GSSG的含量明显增加;CK,LDH和MDA的含量明显降低,同时降低心肌梗死程度,减轻心肌组织学病变。结论 DDQ对离体大鼠缺血/再灌注损伤具有明显的保护作用,此保护作用可能与DDQ提高氧自由基清除能力,减少氧自由基产生,降低脂质过氧化损伤的作用机制有关。     

Effects of the angiotensin II subtype 1 receptor antagonist losartan on functional recovery of isolated rat hearts undergoing global myocardial ischemia-reperfusion

STUDY OBJECTIVE: To investigate the effects of the angiotensin II subtype 1 receptor (AT1R) antagonist losartan on functional recovery of isolated rat hearts undergoing global myocardial ischemia-reperfusion compared with myocardial protective effects of ischemic preconditioning. DESIGN: Ex vivo experiment using isolated perfused rat heart. SETTING: Academic laboratory. INTERVENTION: Hearts from Sprague-Dawley rats were perfused with oxygenated Krebs-Henseleit buffer and randomized to one of four groups: time control, vehicle, ischemic preconditioning, or losartan. MEASUREMENTS AND MAIN RESULTS: After randomization, hearts underwent 30 minutes of global ischemia followed by 30 minutes of reperfusion. Changes in end-diastolic pressure (EDP), left ventricular developed pressure (LVDP), and infarct size were examined between treatment groups by two-way analysis of variance with repeated measures. Cardiac angiotensin II receptor (ATR) density and infarct size were measured in control hearts and in a subgroup of hearts exposed to ischemia-reperfusion injury. Total ATR density and percentage of myocardial AT1R were increased in hearts exposed to ischemia-reperfusion. Myocardial ischemia-reperfusion injury resulted in a 56% reduction in LVDP from baseline in hearts randomized to vehicle. However, it declined by only 22% and 28% in hearts randomized to ischemic preconditioning and losartan, respectively. Compared with vehicle, both ischemic preconditioning and losartan decreased EDP (ischemic preconditioning 39 +/- 3 mm Hg, losartan 54 +/- 5 mm Hg, vs vehicle 78 +/- 8 mm Hg), and reduced infarct size (ischemic preconditioning 9%, losartan 12%, vs vehicle 36%). CONCLUSION: Treatment of isolated rat hearts with losartan before ischemia-reperfusion injury resulted in significant cardioprotection similar to that observed with ischemic preconditioning.     

San酮对大鼠缺血再灌注损伤心肌的保护作用

AIM: To investigate the protective effect of xanthones against myocardial ischemia-reperfusion injury in rats. METHODS: Ischemia-reperfusion injury was induced by 20 min of global ischemia and 40 min of reperfusion in isolated rat hearts or 60-min coronary artery occlusion and 180-min reperfusion in vivo, respectively. Heart rate, coronary flow, left ventricular pressure (LVP), and its first derivative (+/- dp/dtmax) were recorded, and the activity of creatine kinase in coronary effluent and malondialdehyde contents in myocardial tissues were measured in vitro. The activity of serum creatine kinase and myocardium infarct size were measured in vivo. RESULTS: Xanthones (90 or 300 microg/L) caused a significant improvement of cardiac function (LVP and +/- dp/dtmax) and a decrease in the release of creatine kinase in coronary effluent as well as the level of malondialdehyde in myocardial tissues. Xanthones (0.5 or 1.0 mg/kg) also markedly decreased infarct size and the release of creatine kinase in vivo. CONCLUSION: Xanthones protect the myocardium against the damages induced by ischemia-reperfusion in rats, and the effect of xanthones may be related to the inhibition of lipid peroxidation.     

Protective effect of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride on myocardial ischemia-reperfusion injury in rats

The aim of the present study was to investigate the protective effect of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride (DDPH) on myocardial ischemia-reperfusion (I/R) injury in rats and the mechanism of its myocardial protection. For this purpose, 50 Wistar rats were divided into five groups: sham group, control group, verapamil treated group, and two DDPH treated groups (20 and 40 mg/kg, respectively). Myocardial I/R injury model was established by reperfusion for 120 min after 40 min ischemia induced by the ligation of left descending coronary artery in rats. The influence of DDPH on myocardial infarction size was observed and the levels of myocardial enzymes in serum were measured. The activities of oxygen free radical scavenging enzymes and the content of malondialdehyde (MDA) in myocardium and serum were determined. The pathological changes of myocardial tissue were observed. The results showed that DDPH significantly diminished myocardial infarction size, reduced the release of myocardial creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and glutamic oxaloacetic aminotransferase (GOT), protected the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the content of MDA in myocardium and serum as compared with the control group. The degree of myocardial injury was slighter in DDPH treated groups than in control group. These results suggest that DDPH produces a cardioprotective effect during myocardial I/R injury, which may be related to blocking calcium channels and inhibiting the formation of the oxygen free radical and subsequent peroxidation of lipid by DDPH.     

PI3K/Akt信号通路在外源性硫化氢后处理大鼠离体心肌中的作用

目的探讨PI3K/Akt信号通路是否参与硫化氢后处理减轻离体大鼠心肌缺血/再灌注损伤。方法 70只♂Sprague Dawley(SD)大鼠随机分为5组(n=14):缺血/再灌注组(I/R组),硫化氢后处理组(N组),溶媒组(D组),LY294002组(L组),硫化氢后处理+LY294002组(N+L组)。采用离体心脏Langendorff灌注模型,平衡灌注20min后停灌40min复灌60min。记录平衡末及灌注结束时的左室舒张末期压(LVEDP)、左室发展压(LVDP)、左室内压上升最大速率(+dp/dt)、左室内压下降最大速率(-dp/dt)、心率(HR)、冠脉血流量(CF);灌注结束时,TTC法染色心肌切片并计算心肌梗死面积百分比,TUNEL法检测心肌细胞凋亡计算凋亡指数(AI),Western blot半定量p-Akt和总的Akt表达水平。结果平衡灌注末各组间心功能指标(基础值)差异未见统计学意义(P>0.05)。灌注结束时,与I/R组比较,N组可改善再灌注损伤心功能的各项指标(P<0.05),使心肌梗死面积缩小和凋亡指数降低(P<0.05),p-Akt表达水平升高(P<0.05)。LY294002逆转了硫化氢后处理的心功能指标、心肌梗死面积、凋亡指数及p-Akt表达水平(P<0.05),使L组和N+L组p-Akt蛋白表达明显低于N组(P<0.05)。结论外源性硫化氢后处理通过PI3K/Akt信号通路减轻离体大鼠心肌缺血/再灌注损伤。     

Protective effects of demethylbellidifolin on myocardial ischemia-reperfusion injury in rats

The effect of demethylbellidifolin (DMB), a major compound of Swertia davidi Franch, on ischemia-reperfusion injury was studied in rats. Ischemia-reperfusion injury in vivo and in vitro was induced by 20 min of global ischemia followed 40 min of reperfusion and 60 min of coronary artery occlusion followed 180 min of reperfusion, respectively. DMB (100 or 300 microg/L) significantly improved the recovery of cardiac function during reperfusion in isolated rat hearts, as shown by enhancement of coronary flow, left ventricular pressure and its first derivatives (+/-dp/dt(max)). DMB decreased the release of creatine kinase in coronary effluent as well as the level of malondialdehyde in myocardial tissues. In vivo, DMB (0.5 or 1.0 mg/kg) markedly decreased infarct size and the release of creatine kinase. These results suggest that DMB protects the myocardium against damage due to ischemia-reperfusion in rats. The present study also suggests that the effect of DMB may be related to inhibition of lipid peroxidation.     

牛磺酸增强渐增再灌注心肌保护作用的实验研究

目的研究牛磺酸对渐增再灌注处理的离体大鼠缺血/再灌注损伤心肌的保护作用。方法采用Langendorff离体心脏灌流法制备离体大鼠心肌缺血/再灌注模型。SD大鼠随机分为7组:正常对照组(Nor)、缺血/再灌注组(I/R)、渐增再灌注组(GR)、牛磺酸低浓度组(T20)、牛磺酸高浓度组(T40)、渐增再灌注联合牛磺酸低浓度组(GT20)、渐增再灌注联合牛磺酸高浓度组(GT40)。记录平衡末及再灌注90min心功能,TTC染色法测定心肌梗死面积,检测冠脉流出液中乳酸脱氢酶(LDH)活性及心肌组织中Caspase-3活性,TUNEL法检测心肌细胞凋亡。结果与缺血/再灌注组比较,GR、牛磺酸能够改善心功能,减少心肌梗死面积,减少LDH漏出,降低心肌Caspase-3活性并减少心肌细胞凋亡;相比单纯应用GR及牛磺酸,渐增再灌注联合牛磺酸的保护作用更强,且GT40组保护作用最强。结论 GR和牛磺酸均能减轻大鼠离体缺血/再灌注心肌的损伤,牛磺酸,特别是高浓度牛磺酸能够增强渐增再灌注对心肌的保护作用,抗凋亡可能是二者发挥心肌保护作用的机制之一。     

舒血宁注射液对大鼠心肌缺血再灌注损伤的保护作用

目的观察舒血宁对大鼠心肌缺血再灌注(MIR)损伤后的保护作用。方法 30只SD雄性大鼠随机分成假手术组、手术组和舒血宁组。采用结扎左冠状动脉前降支(LAD)复制大鼠心肌缺血再灌注损伤模型,用氯化三苯四唑(TTC)染色法测定心肌梗死面积,测定血浆肌酸激酶(CK-MB)和肌钙蛋白I(cTnI)浓度水平以及心肌组织NO的含量。结果与手术组相比,舒血宁组心肌梗死面积明显减少,并能显著降低血清CK-MB、cTnI浓度以及提高心肌组织NO的含量。结论舒血宁对心肌缺血再灌注损伤有明显的保护作用,可能与提高心肌NO的含量有关。     

间歇性高海拔低氧适应对大鼠缺血耐受的心肌毛细血管生成以及冠脉血流的影响

目的:为了阐述间歇性高海拔低氧对于大鼠心脏冠脉毛细血管以及冠脉血流的影响.方法:利用离体大鼠心脏Langendorff灌流模型来检测缺血复灌期的冠脉流量变化,利用免疫过氧化酶染色测定法和计算机辅助形态计量分析法来测定心脏毛细血管密度.利用放免方法检测心肌中cGMP的水平.结果:缺血前,间歇性低氧适应(IHA)的大鼠的冠脉流量水平(IHA28 13.4mL/min±1.5mL/min,IHA4215.4mL/min±2.0mL/min,P<0.01)要比常氧下的大鼠(11.0±0.8)mL/min高,IHA大鼠在缺血复灌后冠脉流量的恢复也较好.作为适应的结果,IHA大鼠左心室心肌毛细血管密度约为常氧大鼠的1.5倍,但没有发现明显的心室肥大.缺血复灌前后这两组的心肌cGMP的水平都没有改变.然而与常氧大鼠组比较,IHA训练大鼠的cGMP水平明显增加.在离体心脏灌流中,IHA大鼠缺血复灌后心功能的恢复较常氧组好.结论:IHA增加了大鼠心脏对缺血复灌损伤的耐受,IHA诱导的冠脉循环增加以及血管生长可能是IHA心肌保护效应的机制.     

缝隙连接蛋白Cx43介导硫化氢后处理对大鼠心肌的保护作用

目的探讨缝隙连接蛋白Cx43是否参与硫化氢后处理减轻离体大鼠心脏缺血/再灌注(I/R)损伤。方法 72只♂SD大鼠随机分为6组(n=12):空白组(Sham组),缺血/再灌注组(I/R组),溶媒组(DMSO组),抑制剂18β-次甘草酸组(AGA组),硫化氢后处理组(NP组),硫化氢后处理+AGA组(N+A组)。采用离体心脏Langendorff灌注模型,平衡灌注20 min后,停灌30 min,复灌60 min。记录平衡末及灌注结束时的心率(HR)、左室舒张末期压(LV-EDP)、左室发展压(LVDP)、左室内压上升最大速率(+dp/dtmax)、左室内压下降最大速率(-dp/dtmax);灌注结束时,TTC染色法检测心肌梗死面积;Western blot半定量线粒体和胞质总的Cx43(total connexin 43,tCx43)和磷酸化Cx43(phosphorylated connexin 43,pCx43)表达水平。结果平衡灌注末各组间心功能指标差异无统计学意义。再灌注后,与I/R组比较,NP组明显改善再灌注损伤心功能的各项指标(P<0.05),减少心肌梗死面积[(24.4±4.8)%vs(49.4±4.2)%,P<0.05];tCx43表达在线粒体中明显升高,胞质中明显降低,pCx43表达线粒体中明显升高,胞质中明显降低。AGA逆转了硫化氢后处理产生的心肌保护效应及tCx43和pCx43在线粒体中表达的增加(P<0.05)。结论缝隙连接蛋白Cx43参与了硫化氢后处理减轻离体大鼠心脏I/R损伤过程。     

七氟烷预处理对成年及幼年大鼠心肌缺血/再灌注损伤保护作用的对比研究

目的观察比较七氟烷预处理对成年及幼年大鼠心肌缺血/再灌注损伤保护作用及可能机制。方法 36只成年♂SD大鼠随机分为3组:对照组(sham 1组),缺血/再灌注组(I/R 1组),七氟烷预处理组(S 1组);36只幼年♂SD大鼠随机分为3组:对照组(sham 2组),缺血/再灌注组(I/R 2组),七氟烷预处理组(S 2组)。采用Langendorff离体大鼠心肌灌注模型。对照组,自然灌流120 min;缺血/再灌注组,平衡灌注30 min,缺血30 min,复灌60 min;七氟烷组,平衡灌注15 min,含七氟烷的K-H液10 min,洗出5 min,缺血30min,再灌注60 min。记录各组心脏在平衡末及复灌15 min的左室舒张末压(LVEDP)、左室发展压(LVDP)、左室压力升高或降低最大速率(±dp/dtmax)、心率(HR)。复灌15 min时,TUNEL法检测凋亡细胞,免疫印迹法(Western blot)半定量检测p-Akt和总Akt的含量;复灌末TTC法计算心肌梗死面积百分比。结果平衡灌注末各组间心功能指标(基础值)差异未见统计学意义(P>0.05)。灌注结束时,S 1组较I/R 1组以及S 2组较I/R 2组心功能明显改善,心肌梗死面积减少和凋亡指数降低(P<0.05),同时p-Akt表达水平升高(P<0.05)。结论 1 MAC的七氟烷预处理可能通过增强Akt的磷酸化来减轻成年及幼年大鼠的心肌缺血/再灌注损伤。