阿魏酸钠对离体大鼠心脏的药理性预适应保护作用及机制

目的研究阿魏酸钠(sodiumferulate,SF)诱导药理性预适应对离体大鼠心脏的保护作用及其机制。方法将大鼠离体心脏随机分5组:正常组(Control组,富氧液灌注100min);缺氧/复氧损伤组(I/R组,稳定灌流30min,缺血停灌40min后复灌30min);缺血预适应组(IP组,行3次停灌5min、复灌5min刺激后,停灌40min、复灌30min);SF组(用含有1.69mmol.L-1SF的灌流液灌流15min后改用正常灌流液灌流15min,后行停灌40min、复灌30min);格列本脲组(Gli组,用格列本脲30μmol.L-1和SF1.69mmol.L-1合用灌流心脏15min后改用正常灌流液灌流15min,后行停灌40min、复灌30min)。结果与I/R组相比1.69mmol.L-1SF能明显改善心功能、减少心律失常发生率及严重程度、降低心肌组织钙超载、保护心肌Na+,K+-ATP酶、Ca2+ATP酶活性。30μmol.L-1格列本脲与SF合并使用后,上述心肌保护作用则部分取消。结论SF预处理能改善心功能,抗心律失常、抗钙超负荷,其作用机制至少部分与KATP通道开放有关。     

缝隙连接参与缺血后处理和庚醇的心肌保护作用

目的探讨缝隙连接是否参与缺血后处理和庚醇的抗心肌缺血/复灌（I/R）损伤作用。方法采用离体大鼠心脏Langendorff灌流方法,冠脉结扎30 min,复灌120 min复制局部I/R模型,测定心室力学指标和复灌各时间点冠脉流出液中乳酸脱氢酶（LDH）含量。实验结束测定心肌梗死面积。全心停灌30 min,复灌120 min复制全心I/R模型,测定心律失常和心肌传导速度。分别在复灌初期给予缝隙连接脱耦联剂庚醇和缝隙连接开放剂AAP10各15 min。结果在局部缺血/复灌模型上,与I/R组相比,缺血后处理组和庚醇组心肌梗死面积明显减少,复灌期间冠脉流出液中LDH含量降低。同时缺血后处理组明显改善心室力学指标,缓解冠脉流量的减少;在全心缺血/复灌模型上,缺血后处理组和庚醇组在复灌期间的心律失常评分明显下降,心肌传导速度降低。AAP10在局部和全心缺血/复灌模型上明显减弱缺血后处理和庚醇的心肌保护作用。结论缺血后处理和庚醇具有抗心肌缺血/复灌损伤作用,这种保护作用可能与缝隙连接细胞间通讯的减弱有关。     

丹酚酸B对兔离体心脏缺氧再复氧损伤的保护作用

目的观察丹酚酸B对兔离体心脏缺氧-复氧损伤的保护作用。方法离体兔心脏Langendorff灌流,通氮气饱和的灌流液60min后再恢复含氧灌流液灌流60min,造成缺氧-复氧损伤;自动生化分析仪测定冠脉流出液中肌酸激酶(CK)和乳酸脱氢酶(LDH)活性;光学显微镜观察心肌组织结构改变。结果在缺氧的同时给予丹酚酸B0.3,1和3mg.L-l灌流60min,可降低心率,增加冠脉流量,降低冠脉流出液中CK和LDH的水平,心肌组织形态学损伤明显减轻。结论丹酚酸B对兔离体心脏缺氧-复氧损伤有明显的保护作用。     

丹红注射液预处理对大鼠心脏缺血再灌注损伤的保护作用

目的 探讨丹红注射液预处理对大鼠心脏缺血再灌注损伤的保护作用.方法 雄性SD大鼠24只.大鼠心脏离体后悬于Langendorff灌流装置.随机分为3组,每组8只:缺血组(ISCH组):大鼠心脏离体平衡50 min,37℃缺血45 min,K-H液复灌3 h;低浓度丹红注射液预处理组(L-prec组):大鼠心脏平衡20 min,以含低浓度丹红注射液(5 mg/L)的灌注液灌注15 min,洗脱15 min,37℃缺血45 min,K-H液复灌3 h;高浓度丹红注射液预处理组(H-prec组):大鼠心脏平衡20 min,以含高浓度丹红注射液(15 mg/L)的灌注液灌注15 min,洗脱15 min,37℃缺血45 min,K-H液复灌3 h.平衡50 min和复灌2 h 期间连续监测LVDP,LVDEP,±dp/dtmax.复灌60 min时接取冠脉流出液,测定冠脉流出液中CK和LDH的含量.复灌结束,将心脏切片(1～2 mm)并做TTC染色.结果 机械功能:基础状态时3组LVDP,LVDEP,±dp/dtmax两两比较差异无统计学意义(P>0.05).复灌期间L-prec组的LVDP,LVDEP,±dp/dtmax与ISCH组相比,差异无统计学意义.H-prec组的LVDP和±dp/dtmax与ISCH组相比,显著升高(P<0.05);LVDEP与ISCH组相比,显著降低(P<0.05).冠脉生化指标及心梗面积:复灌60 min时L-prec组和H-prec组的CK 和LDH及心梗面积与ISCH组相比,显著性降低(P<0.05);复灌60 min时L-prec组和H-prec组之间CK 和LDH及心梗面积差异无统计学意义(P>0.05).结论 丹红注射液预处理能减轻心肌缺血再灌注损伤后CK和LDH 的释放,缩小心梗面积;高浓度丹红注射液预处理能显著增强心脏缺血再灌注损伤后心脏的机械功能.     

参麦注射液对正常及缺血再灌注离体豚鼠心脏的影响

目的观察参麦注射液(SM)对正常及缺血再灌注离体豚鼠心脏的影响。方法采用正常Langendorff灌流及缺血再灌注离体豚鼠心脏模型,观察SM对冠脉流量的影响,测定冠脉流出液中乳酸脱氢酶(LDH)活性及心肌组织丙二醛(MDA)、超氧化物歧化酶(SOD)的活性。结果SM可显著提高正常及缺血-再灌注离体豚鼠心脏的冠脉流量,减少缺血-再灌注后LDH的漏出总量,降低缺血再灌后心肌组织MDA的含量,升高SOD的活性。结论SM可增加正常及缺血-再灌离体豚鼠心脏冠脉流量,减轻缺血-再灌引起的心肌损伤。     

三味檀香散预处理对大鼠离体心脏缺血-再灌注血流动力学的影响

目的 研究藏药三味檀香散预处理对大鼠离体心脏缺血-再灌注血流动力学的影响.方法 采用Langendorff离体心脏灌流的方法,将大鼠随机分为正常对照组、缺血-再灌组(I/R)组、三味檀香散大、中、小剂量组,除正常对照组以K-H液平衡灌流90 min外,其余各组均平衡灌流30 min、停灌30 min、再灌注30 min,模拟心肌缺血-再灌注损伤;观察不同时间点各组大鼠血流动力学的指标:心率(HR)、左心室收缩压(LVSP)、左心室压力上升和下降最大变化速率(±dp/dt max)、冠脉流量(CF).结果 与正常对照组相比,离体大鼠的心脏停灌30 min、再灌注30 min,可引起明显的心功能抑制.三味檀香散预处理有明显的正性变力作用,大、中、小剂量组的LVSP、±dp/dt max明显高于I/R组(P＜0.05或P＜0.01),各组间的HR和CF无差异(P＞0.05).结论 三味檀香散预处理能有效改善左室的顺应性,增强缺血-再灌注大鼠离体心脏的收缩和舒张功能,对缺血-再灌注损伤大鼠的离体心脏有保护作用.     

内源性硫化氢参与缺血后处理减轻离体大鼠心脏缺血/再灌注损伤

目的探讨内源性硫化氢是否参与缺血后处理减轻大鼠心肌缺血/再灌注损伤。方法Sprague Dawley(SD)大鼠离体心脏Langendorff灌流,平衡20min,全心缺血30min,复氧灌注60min,在复灌即刻给与短暂停灌15s/复灌15 s循环4次造成心肌缺血后处理模型。预先给予胱硫醚-γ-裂解酶(cystanthionine-γ-lysase,CSE)抑制剂炔丙基甘氨酸(L-propargylglycine,PAG),以及给予PAG后加用外源性硫化氢供体NaHS后处理,观察它们对缺血后处理的影响。记录心率(HR)、左室发展压(LVDP)、冠脉流出量(CF);检测灌流液中乳酸脱氢酶(LDH)活性、心肌组织CSE活性、硫化氢的含量以及心肌梗死面积。结果缺血/再灌注组LVDP下降、冠脉灌流液中LDH活性明显增加、心肌梗死面积增加(vsControl组,P<0.05)。缺血后处理组LVDP升高、冠脉灌流液中LDH活性下降、心肌梗死面积缩小(vsIR组,P<0.05)。PAG加缺血后处理组心肌CSE活性及H2S生成下降、并且逆转了缺血后处理的作用,而外源性硫化氢供体NaHS后处理组H2S生成回升、LVDP升高、心肌梗死面积缩小(vsIR组,P<0.05)。结论内源性硫化氢参与大鼠心肌缺血后处理减轻缺血/再灌注损伤。     

线粒体乙醛脱氢酶2在心肌缺血后处理中的作用

目的探讨线粒体乙醛脱氢酶2(aldehyde dehydrogen-ase 2,ALDH2)在离体大鼠心肌缺血后处理中的保护作用。方法采用离体大鼠心脏Langendorff灌流方法 ,局部结扎冠状动脉左前降支30min,复灌120min模拟心肌缺血/复灌模型。缺血后处理采用复灌初期立即给予反复6次的10s复灌/10s全心缺血的循环。测定心室动力学指标和复灌期间冠脉流出液中乳酸脱氢酶(lactate dehydrogenase,LDH)含量。实验结束后TTC染色法测定心肌梗死面积。RT-PCR测定左心室前壁心尖组织线粒体ALDH2、Bcl-2和Bax mR-NA的表达。结果与单纯缺血/复灌组相比,缺血后处理明显促进左室发展压、左室做功的恢复,降低复灌期冠脉流出液中LDH的释放和心肌梗死面积,ALDH2 mRNA表达增高,Bcl-2/Bax mRNA比值增高。ALDH2阻断剂氨基氰减弱了缺血后处理的作用。结论缺血后处理部分通过增强线粒体乙醛脱氢酶2的表达发挥心肌保护作用。     

莲房原花青素对大鼠心肌缺血再灌注损伤的保护作用

目的探讨莲房原花青素(LSPC)对大鼠心肌缺血再灌注损伤的作用。方法用麻醉大鼠冠脉结扎30 min后，再灌注45 min造成心肌损伤模型。离体大鼠心脏经停灌30 min后，用正常K-H液复灌30 min，造成心肌损伤模型。均于实验前给予药物或生理盐水。结果LSPC可降低复灌后血清ET和Ang II的浓度，抑制MDA含量升高，并保持SOD活性及NO的水平。心脏复灌以后冠脉流量和心率明显恢复，心肌细胞酶CK和LDH漏出减少，心肌组织黄嘌呤氧化酶(XO)的活性降低，心肌超微结构的病理变化改善等。结论LSPC对整体及离体大鼠心肌缺血再灌注损伤具有保护作用。     

咖啡酸苯乙酯对大鼠离体心脏心肌缺血再灌注的保护作用北大核心CSCD

目的建立大鼠离体心脏心肌缺血再灌注模型,初步探讨咖啡酸苯乙酯对离体心脏心肌缺血再灌注损伤的保护作用。方法雄性SD大鼠30只,取心脏Langendorff法离体灌流,实验分5组:空白组:KH(Krebs-Henseleit)液连续灌流100 min;模型组:KH液稳灌30 min后停灌30 min,再灌注KH液40 min;给药组:KH液稳灌30 min后,停灌30 min,再灌注3、6和12 mg/L CAPE的KH液40min。实验中观察各组大鼠离体心脏的冠脉流量、心肌收缩力及心率的变化。停灌后测其各组心肌组织的丙二醛(MDA)、蛋白羰基化(PCO)的含量和超氧化物歧化酶(SOD)活性。结果心脏缺血再灌注期间,模型组收缩力减弱,张力增加,心率减慢,冠脉流量明显减少,出现心律失常;给药组在再灌注后收缩力增强,张力降低,心率增快,冠脉流量明显增加,节律整齐。停灌后模型组MDA、PCO含量明显升高,SOD含量降低,而给药组MDA、PCO的含量较模型组减少(P<0.01),且减少SOD含量的降低(P<0.01)。说明缺血再灌注能够增加心脏的氧化应激,诱导氧化损伤,CAPE保护可以减少氧化损伤,且呈剂量依赖性。结论咖啡酸苯乙酯对大鼠离体心脏缺血再灌注损伤具有保护作用,其机制可能与抗氧化作用有关。     

Evidence of the role of angiotensin AT(1) receptors in remote renal preconditioning of myocardium

The underlying mechanisms of myocardial preconditioning after a brief period of renal ischemia-reperfusion are unknown. The phenomenon itself and the involvement of AT(1) angiotensin receptors was therefore investigated using an in vivo rat model of acute myocardial infarction. Anesthetized rats underwent a left thoracotomy and pericardiotomy. A laparotomy was performed to expose the left renal artery. Animals were then preconditioned with four episodes, each consisting of 5 min of renal artery occlusion followed by 10 min of reperfusion, or underwent a 60 min sham period of anesthesia. Subsequently, the left coronary artery was occluded for 30 min and reperfused for 2 h. Area at risk and infarct size was estimated along with hemodynamic and temperature data recording. The infarct-to-risk ratio was limited from 56.36 +/- 2.36 and 50.65 +/- 4.71 in control to 12.0 +/- 0.48 and 12.57 +/- 0.44 in preconditioned hearts, by volume and weight methods. The protective effect of renal preconditioning on the myocardium was not abolished by losartan 1 mg/kg (10.11 +/- 0.12 and 11.2 +/- 1.4) pretreatment whereas it was completely attenuated by losartan 5 mg/kg (46.5 +/- 1.0 and 47.8 +/- 1.4) administration. Thus we can infer that angiotensin AT(1) receptors participate in renal preconditioning of the myocardium in in vivo rat hearts.     

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.     

Negative metabolic effects of cGMP are enhanced in obese rat hearts

Leptin resistance leads to obesity and may affect responses to the second messenger cGMP. We tested the hypothesis that the myocardial negative metabolic response to cGMP would be enhanced in leptin-resistant animals. This hypothesis was tested in anesthetized open-chest Zucker obese (n = 16) and age-matched control rats (n = 13). Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) measurements were used to determine myocardial O2 consumption (VO2). Protein phosphorylation by cGMP protein kinase and cAMP phosphodiesterase activity were also determined. Either vehicle (saline) or 8-Br-cGMP (10(-3) M) was topically applied to the left ventricular surface. Body weight was significantly greater in the obese rats (523 +/- 17 versus 322 +/- 12 g). There were no hemodynamic differences between groups. There was no difference in VO2 between lean (52 +/- 13 mL O2/min/100 g) and obese (54 +/- 9) vehicle-treated rats. 8-Br-cGMP significantly lowered VO2 in obese (35 +/- 6) but not lean (45 +/- 7) rats. This was not related to altered protein phosphorylation by the cGMP protein kinase. Cyclic GMP inhibited cAMP phosphodiesterase activity in lean but not obese hearts. Thus, the high myocardial oxygen consumption of lean rats was not significantly affected by cGMP but was reduced in obese hearts. This appeared to be related to a reduced inhibition of cAMP phosphodiesterase activity by cGMP in the Zucker obese rat.     

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。     

1-（2，6-二甲基苯氧基）-2-（3，4-二甲氧基苯乙氨基）丙烷盐酸盐对大鼠离体心脏缺血再灌注损伤的保护作用

研究1-（2,6-二甲基苯氧基）-2-（3,4-二甲氧基苯乙氨基）丙烷盐酸盐（DDPH）对大鼠离体心脏缺血再灌注损伤的保护作用。方法：采用Langendorff大鼠离体心脏灌流技术,结扎冠状动脉前降支（LAD）40min,复灌120min后复制出大鼠离体心脏缺血再灌注损伤模型,观察DDPH对大鼠离体心脏左心室功能、心肌梗死范围、脂质过氧化及超微结构损伤的影响。结果：DDPH能显著改善大鼠离体心脏左心室功能,明显缩小心肌梗死范围,能显著提高大鼠心肌组织中超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH—Px）活性,降低心肌脂质过氧化代谢产物丙二醛（MDA）含量,减少心肌超微结构损伤。结论：DDPH对大鼠离体心脏缺血再灌注损伤有保护作用,其作用机制可能与抑制氧自由基的生成和脂质过氧化作用有关。     

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.     

Edaravone prevented deteriorated cardiac function after myocardial ischemia-reperfusion via inhibiting lipid peroxidation in rat

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has potent effects in the brain as a free radical scavenger in ischemia-reperfusion as well as in ischemic injuries. However, whether this free radical scavenger prevents deterioration of cardiac function and lethal ventricular arrhythmias after ischemia-reperfusion in rat heart is not clear. We aimed to assess whether free radical scavenging by edaravone maintains cardiac function and suppresses life-threatening ventricular tachyarrhythmia after myocardial ischemia-reperfusion. Twenty-nine 7-week-old male Sprague-Dawley rats had acute myocardial ischemia induced by ligation of the left coronary artery for 5 minutes followed by reperfusion. Eleven were treated by intravenous injection of edaravone at 3 mg/kg 2 minutes after coronary ligation, and 18 were left untreated. The index of systolic function (contractility; end-systolic elastance, Ees) and hemodynamics were measured by pressure-volume relationships every 5 minutes before ligation to 25 minutes after reperfusion. Blood levels of malondialdehyde (MDA) and the ischemic areas were also measured 25 minutes after reperfusion. There were no differences in the ischemic areas between the groups. Lethal reperfusion tachyarrhythmia was observed in 5 untreated rats but not in those having edaravone treatment. Ees was significantly greater in the edaravone-treated than in untreated rats from 5 to 25 minutes after reperfusion (1789 +/- 866 in untreated versus 2809 +/- 273 mm Hg/mL in edaravone-treated rats at 25 minutes, P < 0.001). MDA level was significantly lower in edaravone-treated than in untreated rats (1.44 +/- 0.29 nmol/L in edaravone-treated versus 1.90 +/- 0.28 nmol/L in untreated group, P < 0.05). The results suggest that edaravone treatment before reperfusion prevented lethal reperfusion ventricular tachyarrhythmias and deteriorated cardiac function with ischemia and ischemia-reperfusion injuries through inhibiting lipid peroxidation in terms of scavenging for free radicals.     

Dimethyl fumarate, a small molecule drug for psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats

Persistent Nuclear Factor-kappaB (NF-kappaB) activation is hypothesized to contribute to myocardial injuries following ischemia-reperfusion. Because inhibition or control of NF-kappaB signaling in the heart probably confers cardioprotection, we determined the potency of the NF-kappaB inhibitor dimethyl fumarate (DMF) in cardiovascular cells, and determined whether administration of DMF translates into beneficial effects in an animal model of myocardial infarction. In rat heart endothelial cells (RHEC), we analysed inhibitory effects of DMF on NF-kappaB using shift assay and immunohistofluorescence. In in vivo experiments, male Sprague Dawley rats undergoing left coronary artery occlusion for 45 min received either DMF (10 mg/kg body weight) or vehicle 90 min before ischemia as well as immediately before ischemia. After 120 min of reperfusion, the hearts were stained with phthalocyanine blue dye and triphenyltetrazolium chloride. Additionally, acute hemodynamic and electrophysiologic effects of DMF were determined in dose-response experiments in isolated perfused rat hearts. DMF inhibited TNF-alpha-induced nuclear entry of NF-kappaB in RHEC. In in vivo experiments, myocardial infarct size was significantly smaller in rats that had received DMF (20.7%+/-9.7% in % of risk area; n=17) than in control rats (28.2%+/-6.2%; n=15). Dose-response experiments in isolated perfused rat hearts excluded acute hemodynamic or electrophysiologic effects as mechanisms for the effects of DMF. DMF inhibits nuclear entry of NF-kappaB in RHEC and reduces myocardial infarct size after ischemia and reperfusion in rats in vivo. There was no indication that the beneficial effects of DMF were due to acute hemodynamic or electrophysiologic influences.     

The protective effects of ligustrazine on ischemia-reperfusion and DPPH free radical-induced myocardial injury in isolated rat hearts

Previous investigations have suggested that tumor necrosis factor-alpha (TNF-alpha) can contribute to myocardial damage during ischemia-reperfusion. In the present study, we examined whether the cardioprotective effects of ligustrazine are related to inhibition of TNF-alpha production in the rat models of ischemia-reperfusion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-induced myocardial injury. Ischemia for 20 min and reperfusion for 40 min caused a decline in cardiac function (left ventricular pressure, +/- d p/d t(max), heart rate and coronary flow) and an increase in the release of creatine kinase in coronary effluent and the content of TNF-alpha in myocardial tissues. Similarly, perfusion with DPPH (100 nM) for 30 min significantly decreased cardiac function, and increased the release of creatine kinase and the content of TNF-alpha. Ligustrazine at the concentration of 40 or 80 mg/L markedly improved cardiac function and reduced the release of creatine kinase and the content of TNF-alpha in myocardial tissues in hearts subjected to ischemia-reperfusion or DPPH perfusion. These results suggest that the cardioprotection afforded by ligustrazine is related to a reduction of TNF-alpha content by inhibition of free radical production in isolated rat hearts.