白介素8和兔心肌缺血/再灌注损伤研究

目的 探讨白介素8(rhIL-8)参与兔心肌缺血/再灌注损伤的机制,为减轻再灌注损伤探索新的治疗途径。方法 结扎兔冠状动脉左前降支(left anterior descending coronary artery,LAD)造成缺血1小时,再灌注3.5小时。实验分两组:缺血/再灌注组(MI/R,n=8)和假结扎组(Sham MI/R,n=8)。结果 MI/R组发生严重的心肌损伤,包括受累心肌髓过氧化物酶(myeloperoxidase,MPO)活性增大和血清肌酸磷酸激酶-MB同工酶(CPK-MB)、异构前列腺素(eoi-PGF_(2α))水平增高(均P<0.01)。血清IL-8浓度逐渐升高,免疫组化示受损心肌区血管内皮基底膜呈IL-8阳性染色。结论 血管内皮细胞释放的IL-8是吸引中性粒细胞浸润于缺血区心肌,造成缺血/再灌注损伤的因素之一。     

卡托普利后处理对再灌注损伤鼠肺血管紧张

目的探讨卡托普利后处理对大鼠肺缺血—再灌注时肺血管内皮血管紧张素转换酶(ACE)mRNA表达的影响,分析其可能的作用机制。方法实验大鼠24只,随机分为假手术组(Sham组,n=8只)、缺血—再灌注组(I/R组,n=8只)和卡托普利后处理组(CAP组,n=8只)。I/R组阻断左肺门1 h后,恢复通气再灌注1 h。Sham组开胸游离左肺门,通气及灌注2 h。CAP组于再灌注前20 min腹腔注射卡托普利(10 mg.kg-1)行药物后处理,恢复通气再灌注1 h。留取静脉血及左侧肺组织,分别测定肺组织中髓过氧化物酶(MPO)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量、ACE mRNA的表达量及静脉血中ET-1的含量,测肺湿/干重比(W/D)及光镜下观察肺组织病理变化。结果 CAP组肺组织MPO、MDA的含量及ACE mRNA的表达量、血清ET-1含量及肺W/D明显低于I/R组(P0.05);CAP组肺组织中SOD含量明显高于I/R组(P0.05);CAP组肺组织形态学损伤较I/R组明显减轻。结论卡托普利后处理可以明显减轻鼠肺缺血再灌注损伤,其机制可能与其抑制缺血再灌注损伤鼠肺组织中ACE mRNA的表达有关。     

大鼠急性肾缺血再灌注时心肌细胞氧化损伤及瑞芬太尼的干预作用

目的观察大鼠急性肾缺血再灌注时心肌细胞氧化损伤以及瑞芬太尼预处理对氧化损伤的干预作用。方法建立大鼠肾缺血再灌注损伤模型。将54只Wistar大鼠随机分为假手术组(Sham组)、缺血再灌注组(I/R组)、瑞芬太尼预处理组(R组)。Sham组只结扎单侧肾脏,另一侧只穿线不结扎;I/R组结扎右侧肾脏,动脉夹夹闭左侧肾蒂45min后开放,于再灌注30min、1、2、3h处死大鼠;R组为缺血前以1μg·kg-1·min-1微泵输注瑞芬太尼30min进行预处理,余同I/R组。分别检测各组大鼠心肌组织超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量及谷胱甘肽过氧物酶(GSH-Px)活力变化。结果I/R组、R组与Sham组相比,心肌组织MDA含量升高,SOD、GSH-Px活力降低,且在1、2、3h时间点,差异均有统计学意义(P<0.05)。R组与I/R组比较,心肌组织MDA含量降低,SOD、GSH-Px的表达增高,且差异有统计学意义(P<0.05)。结论大鼠急性肾缺血再灌注可造成心肌细胞氧化损伤,而瑞芬太尼预处理可起到一定的保护作用。     

己酮可可碱在大鼠肠缺血再灌注损伤中的保护作用及机制

目的:探讨己酮可可碱(pentoxifylline,PTX)在大鼠肠缺血再灌注损伤中的保护作用及机制。方法:Wistar大鼠48只随机分成6组,每组8只。(1)假手术组(S); (2)缺血组(I); (3 )缺血再灌注2h组(IR2h); (4)缺血再灌注4h组(IR4h);(5)缺血再灌注2h+PTX组(P2 ); (6)缺血再灌注4h+PTX组(P4 ),测定各组动物血清肿瘤坏死因子α(TNF α)水平、肠组织细胞粘附分子(ICAM 1 )表达、肠组织过氧化物酶(MPO)活性及观察病理形态。结果:IR2h及IR4h组大鼠血清TNF α水平、肠组织ICAM 1表达及肠MPO活性均明显高于S组(P<0. 01)。给予PTX后, 血清TNF α水平有所下降,P4 组与IR4h组比较差异有非常显著意义(P<0. 01);肠组织MPO活性明显降低,IR2h组与P2 组比较或IR4h组与P4 组比较差异均有非常显著意义(P<0. 01);肠组织ICAM 1积分光密度值比较,P2,P4 组明显低于IR2h及IR4h组(P<0. 01)。结论:已酮可可碱可降低血TNF α水平及肠组织ICAM 1表达,减轻中性粒细胞在肠内聚集、活化,从而防治肠缺血再灌注损伤。     

血必净对大鼠肝缺血-再灌注后急性肺损伤的保护作用

目的观察肝脏缺血-再灌注后急性肺损伤的发病机制及血必净对其的干预作用。方法将健康雄性Wistar大鼠90只随机分3组:假手术组(SOG组)30只,缺血再灌注组(I/R组)30只,血必净组(XBJ组)组30只。XBJ组术前3d经尾静脉注射血必净注射液5ml·kg-1·d-1。于再灌注6h、12h、24h各组分别随机选取10只大鼠进行标本检测:观察大鼠肺脏组织病理切片;取新鲜肺组织测定湿/干重比(W/D)、肺组织髓过氧化物酶(MPO)含量,取动脉血检测血气分析(PaO2)。结果XBJ组较I/R组在相同时相点的肺脏病理改变较轻,MPO含量显著降低(P<0.01);W/D显著降低(P<0.01);PaO2升高(P<0.05)。结论血必净注射液对肝脏缺血-再灌注后急性肺损伤具有保护作用,该作用与抑制中性粒细胞在肺内集聚、减少氧自由基的产生有关。     

缺血后适应的心肌保护作用及其对心肌血红素氧化酶-1表达的影响

目的观察新西兰大白兔缺血后适应的心肌保护作用,并对其机制进行探讨。方法采用结扎冠状动脉前降支根部行30min缺血／3h再灌注．制作缺血／再灌注模型。随机分为两组：（1）缺血再灌注组（Con组）;（2）缺血后适应组（PC组）：再灌注时行3次10s复流／10s闭合操作;每组随机抽取6只测定心肌梗死面积及测定血清CK、MPO、MDA、SOD、NOS含量：其余6只测定心肌超微结构的变化,及通过免疫组化方法观察对心脏血红素氧化酶-1（HO—1）蛋白表达的影响。结果PC组可以显著降低缺血再灌注心律失常,缩小心肌梗死面积．降低血清再灌注1h、2h、3hCK值,降低MPO、MDA活性,升高SOD、NOS活性。PC组可以显著改善心肌超微结构损伤．并可上调心肌HO-1的表达。结论缺血后适应可以产生强大的心肌保护作用,心肌HO-1表．达的上调可能与缺血后适应心肌保护作用有关。     

卡巴胆碱减轻肠缺血/再灌注大鼠中性粒细胞活化和多器官损伤

目的探讨胆碱能激动剂——卡巴胆碱对肠缺血/再灌注大鼠中性粒细胞活化的影响及其对脏器功能的保护作用。方法雄性Wistar大鼠随机分为假手术组(N)、肠缺血/再灌注组(I/R)及卡巴胆碱组(Car)。夹闭肠系膜上动脉45min后恢复灌流制成肠I/R模型;卡巴胆碱组在肠缺血15min后经幽门注射卡巴胆碱(100μg/kg体质量)。于缺血45min(I45)、再灌注1h(R1)、2h(R2)、6h(R6)取肠系膜上静脉血进行中性粒细胞(PMN)计数、测定PMN呼吸爆发强度、检测反映脏器功能的血浆酶学指标以及肠和肺组织髓过氧化物酶(MPO)活性。结果肠缺血45min,PMN计数下降,再灌注后逐渐回升,至R6时达高峰。Car组PMN计数在R2和R6时显著低于I/R组大鼠;PMN呼吸爆发强度的变化规律与PMN计数一致。相关分析表明,PMN化学发光峰值变化和血PMN计数的变化呈正相关(r=0.748,P<0.05)。大鼠小肠组织MPO活性在肠缺血和再灌注均升高(P<0.05),R6达最高;Car组小肠MPO活性在肠I/R各时间点均显著低于I/R组(P<0.05～P<0.01)。肺组织MPO活性在肠缺血期降低,再灌注后逐渐升高,在R6时MPO活性达高峰(P<0.01),而此时Car组大鼠肺组织MPO活性仅为I/R组的31%(P<0.01),接近N组。GI/R组大鼠血浆天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、肌酐(Cr)、肌酸激酶-同工酶(CK-MB)在肠缺血后均升高,R2时达峰值(P<0.01),R6时仍高于N组(P<0.05)。Car组大鼠各指标在再灌注后均较I/R组同时相点低,以R2组效果最明显(P<0.01)。结论卡巴胆碱能显著抑制PMN活化,减轻GI/R引起的多脏器功能损伤。     

三氯化钆对肝缺血再灌注损伤的影响

目的探讨库普弗细胞(KCs)功能封闭对肝缺血再灌注损伤的影响。方法雄性Wistar大鼠随机分为三组:对照组:只开腹,不做其他任何处理;缺血再灌注(I/R)组:术前24,48h经鼠尾静脉注射等量0.9%氯化钠溶液(pH3.5);三氯化钆(GdCl3)+I/R组:术前24,48h经鼠尾静脉注射0.5%GdCl3溶液(10mg/kg)。第3天进行肝脏部分缺血再灌注手术(约70%肝血流)。缺血45min后,再灌注3,6h,乙醚麻醉后,开腹进行无菌无热源腹主动脉采血,肝左叶用10%甲醛溶液固定,肝中叶包裹后置-70℃冰箱保存,制备匀浆用于丙二醛(MDA)、谷胱甘肽(GSH)、肿瘤坏死因子(TNF)-α含量的测定。结果缺血45min后,再灌注3,6h,GdCl3+I/R组血浆丙氨酸转氨酶活性、肝脏MDA及TNF-α含量均显著低于I/R组(P<0.01),而GSH含量则明显高于肝损伤组(P<0.01)。结论GdCl3可保护肝缺血再灌注损伤。     

盐酸替罗非班对兔心肌缺血再灌注损伤的影响

目的:探讨盐酸替罗非班(tirofiban hydrochloride,TH)在兔心肌缺血再灌注(ischemia reperfusion,IR)损伤中的作用及其机制。方法:30只雄性新西兰大白兔随机分为3组:假手术组(S组)、心肌I/R模型组(I/R组)和心肌I/R+盐酸替罗非班治疗组(I/R+TH组),每组10只。采用结扎冠状动脉前降支1h后恢复血供的方法制备心肌I/R损伤模型,再灌注0、1、2、4h分别收集血样,酶联免疫吸附法(ELISA)测定血清中肌钙蛋白T(TnT)及炎症因子(IL-32、TNF-α及IL-1β)的水平,再灌注后4h处死动物,化学比色法检测心脏组织中髓过氧化物酶(MPO)的活性。结果:TnT水平,再灌注4h,I/R、I/R+TH组均较S组显著升高(P0.05);炎症因子水平,缺血再灌注后I/R、I/R+TH组均较S组显著升高(P0.05),I/R+TH组在再灌注1、2h有明显改善,组间两两比较,差异有统计学意义(P0.05);MPO活性,与S组比较,I/R组显著增强(P0.05),I/R+TH组差异无统计学意义(P0.05)。结论:盐酸替罗非班对兔心肌I/R损伤具有保护作用,其机制与减少炎症因子释放、降低MPO活性,抑制中性粒细胞聚集有关。     

宫内急性缺血及再灌注对胎鼠肾SOD和MDA的影响

目的利用大鼠宫内急性缺血及再灌注模型检测胎龄21d鼠肾损伤后超氧化物歧化酶(SOD)、丙二醛(MDA)的变化,以探讨宫内缺血/再灌注时肾损伤的发病机制。方法选取孕21dWistar大鼠,腹腔麻醉后,暴露双角子宫及供应子宫和卵巢的动静脉血管,钳夹其双角子宫一侧动静脉血管,钳夹时间分别为10、30min,达要求时间后取下动脉夹行再灌注,再灌注时间分别为0.5、2、6、24h,对侧未钳夹宫角内的胎鼠为对照组,每个时间点留取7份标本。分别检测各个时间点胎鼠肾SOD、MDA的含量。结果①SOD活性:缺血10min时SOD活性开始降低(P>0.05),缺血30min时SOD活性下降明显(P<0.05),随再灌注时间的延长,SOD活性逐渐降低,于再灌注6h时达最低(P<0.01),而后SOD活性开始升高,再灌注24h时虽未恢复正常,但与假手术组无差异(P>0.05);缺血10min组与缺血30min组相比,后组明显低于前组,尤为再灌注0.5h和再灌注6h(P<0.01);②MDA含量:缺血10minMDA含量即开始升高(P>0.05),缺血30min时MDA含量升高明显(P<0.05);随再灌注时间的延长,MDA含量逐渐升高,尤为再灌注2、6、24h(P<0.01);缺血10min组与缺血30min组相比,后组明显高于前组,尤为再灌注6h(P<0.01)。结论宫内缺血无再灌注时即有自由基损伤的存在;自由基损伤可能是宫内缺血再灌注肾损伤的发病机制之一。     

Cardioprotective effects of the vasodilator/beta-adrenoceptor blocker, carvedilol, in two models of myocardial infarction in the rat.

The purpose of this study was to evaluate the cardioprotective effects of carvedilol, a beta-adrenergic blocker and vasodilator, in two models of ischemic myocardial damage in the rat. Following coronary artery occlusion for 0.5 h and reperfusion for 24 h (MI/R group), left ventricular (LV) injury was determined by planimetric analysis of triphenyltetrazolium chloride-stained tissue, and polymorphonuclear leukocyte infiltration was assessed by measuring myeloperoxidase (MPO) activity. In the vehicle-treated MI/R group, infarct size was 14.2 +/- 1.3% of the LV (n = 16), and MPO activity was increased to 2.8 +/- 0.7 from 0.14 +/- 0.03 U/g tissue in the vehicle-treated sham-occluded group (p less than 0.01). Carvedilol (1 mg/kg i.v., 15 min prior to coronary artery occlusion and at 3.5 h following reperfusion) reduced myocardial infarct size to 7.5 +/- 1.2% of the LV (n = 14; p less than 0.01) and attenuated the increase in MPO activity to 1.4 +/- 0.4 U/g tissue (p less than 0.05). A lower dose of carvedilol (i.e. 0.3 mg/kg i.v.) did not limit myocardial infarct size or the increase in MPO activity. In a model of permanent coronary artery occlusion, 24-hour survival was reduced from 85% in sham-occluded animals (n = 38) to 44% in the vehicle-treated MI group (n = 84; p less than 0.01). In comparison to the vehicle-treated MI group, carvedilol (0.3 mg/kg i.v., 15 min prior to coronary artery occlusion and 1 mg/kg 4 h after occlusion) improved survival by 55% (n = 64; p less than 0.05, compared to the vehicle-treated MI group), whereas the same dose of propranolol (n = 42) had no significant effect on survival. These results indicate that carvedilol reduces myocardial ischemia/reperfusion injury, and significantly improves survival in a permanent coronary artery occlusion model of myocardial infarction.     

Cyclosporin-A reduces leukocyte accumulation and protects against myocardial ischaemia reperfusion injury in rats

The present study was designed to evaluate the effect of cyclosporin A in a rat model of myocardial ischaemia reperfusion injury (MI/R). Anaesthetized rats were subjected to total occlusion (20 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham myocardial ischaemia-reperfusion rats (Sham MI/R) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity (MPO), serum creatinine phosphokinase activity (CPK), serum tumor necrosis factor (TNF-α), cardiac mRNA for TNF-α, cardiac intercellular adhesion molecule-1 (ICAM-1) immunostaining and myocardial contractility (left ventricle dP/dt_max) were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum CPK activity and myeloperoxidase activity (a marker of leukocyte accumulation) both in the area-at-risk and in the necrotic area, reduced myocardial contractility and induced a marked increase in the serum levels of the TNF-α. Furthermore increased cardiac mRNA for TNF-α was measurable within 10 to 20 min of left main coronary artery occlusion in the area-at-risk and increased levels were generally sustained for 0.5 h. Finally, myocardial ischaemia-reperfusion injury increased ICAM-1 staining in the myocardium. Administration of cyclosporin A (0.25, 0.5 and 1 mg/kg as an i.v. infusion 5 min after coronary artery occlusion) lowered myocardial necrosis and myeloperoxidase activity in the area-at-risk and in the necrotic area, decreased serum CPK activity, increased myocardial contractility, reduced serum levels of TNF-α and the cardiac cytokine mRNA levels, and blunted ICAM-1 immunostaining in the injured myocardium. The data suggest that cyclosporin A suppresses leukocyte accumulation and protects against myocardial ischaemia-reperfusion injury.     

Reduction in myocardial ischemic/reperfusion injury and neutrophil accumulation after therapeutic administration of streptokinase.

The benefit of thrombolytic agents to reduce myocardial infarct size, improve left ventricular (LV) function, and prolong survival in human subjects is generally recognized, although the precise mechanism is poorly defined. This study was designed to evaluate the cardioprotective effects of streptokinase (SK) in rats, a species less responsive to plasminogen activators, using a model of mechanical occlusion and release of the left coronary artery. Myocardial injury and polymorphonuclear leukocyte (PMN) infiltration were determined by measuring creatine phosphokinase (CPK) specific activity and myeloperoxidase (MPO) activity, respectively, in the LV free wall (LVFW). After coronary artery occlusion for 0.5 h and reperfusion for 24 h (myocardial ischemia, MI/R), CPK specific activity decreased from 7.0 +/- 0.3 U/mg protein in the sham + vehicle group to 5.6 +/- 0.5 U/mg protein in the MI/R + vehicle group (n = 19, p less than 0.01), while MPO activity increased from 0.14 +/- 0.03 U/g tissue in the sham + vehicle group to 2.8 +/- 0.7 U/g in the MI/R + vehicle group (p less than 0.001). Administration of SK (100,000 IU/kg + 50,000 IU/kg/h for 2 h beginning 15 min before coronary artery reperfusion) reduced the loss of CPK specific activity from reperfused myocardium (6.8 +/- 0.5 U/mg protein, n = 23, p less than 0.05 as compared with the MI/R + vehicle group) and attenuated the increase in MPO activity (1.3 +/- 0.4 U/g tissue, p less than 0.05 as compared with the MI/R + vehicle group). This dose of SK did not change plasma fibrinogen concentration, slightly reduced plasminogen activity (i.e., 20% from control value), and markedly reduced alpha 2-antiplasmin activity (i.e., 60% from control values). A lower dose of SK (i.e., 10,000 IU/kg + 5,000 IU/kg/h for 2 h) did not reduce myocardial injury, did not attenuate the increase in MPO activity, and had no effect on the measured hemostatic parameters. Survival in all MI/R groups ranged from 62 to 66%, and there were no differences in survival between any of the groups (p greater than 0.05). In a model of arachidonic acid-induced rat hindpaw inflammation, SK had no effect on the increase in MPO activity, suggesting that the increase in myocardial MPO activity was not due to a direct effect on inflammatory cell accumulation. In in vitro studies, SK (1-1,000 U/ml) did not scavenge superoxide anion produced by purine (10 mM) and xanthine oxidase (10 mU/ml), nor did it reduce superoxide release, beta-glucuronidase release, or neutrophil aggregation of rabbit peritoneal neutrophils activated with fMLP.(ABSTRACT TRUNCATED AT 400 WORDS)     

阿魏酸钠保护大鼠心肌缺血再灌注损伤的作用机制研究

目的 探讨阿魏酸钠(SF)对心肌缺血再灌注(MI/R)损伤大鼠的保护作用及其机制.方法 40只SD大鼠随机分为假手术组、模型组、SF高剂量组(40 mg/kg)、SF低剂量组(20 mg/kg),每组10只.采用结扎左冠状动脉前降支30 min再灌注2 h的方法 复制MI/R损伤大鼠模型,造模成功后取心脏测定心肌梗死面积、心肌组织细胞间黏附分子-1(ICAM-1)和核因子-κB(NF-κB)表达情况及髓过氧化物酶(MPO)的活力.结果 SF高、低剂量组心肌梗死面积小于模型组(P<0.05,P<0.01).模型组心肌MPO活力和ICAM-1、NF-κB阳性表达率高于假手术组,SF高、低剂量组均低于模型组(P<0.05,P<0.01).结论 SF对心肌MI/R损伤的保护作用是通过抑制中性粒细胞浸润,下调NF-κB和ICAM-1的表达,抑制炎性反应等途径实现的.     

Pterostilbene protects against myocardial ischemia/reperfusion injury via suppressing oxidative/nitrative stress and inflammatory response

Recent studies have shown that pterostilbene (Pte) confers protection against myocardial ischemia/reperfusion injury. The oxidative/nitrative stress and inflammation induce injury after myocardial ischemia/reperfusion. The present study was designed to evaluate whether treatment with Pte attenuates oxidative/nitrative stress and inflammation in myocardial ischemia/reperfusion (MI/R). Rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion, and the rats were administered with vehicle or Pte. The results showed that Pte (10 mg/kg) dramatically improved cardiac function and reduced myocardial infarction and myocardial apoptosis following MI/R. As an indicator of oxidative/nitrative stress, myocardial ONOO⁻ content was markedly reduced after Pte treatment. And, Pte led to a dramatic decrease in superoxide generation and malondialdehyde (MDA) content and a dramatic increase in superoxide dismutase (SOD) activity. In addition, Pte treatment significantly reduced p38 MAPK activation and the expression of iNOS and gp91^phox and increased phosphorylated eNOS expression. Pte treatment dramatically decreased myocardial TNF-α, and IL-1β levels and myeloperoxidase (MPO) activity. Furthermore, ONOO⁻ suppression by either Pte or uric acid (UA), an ONOO⁻ scavenger, reduced myocardial injury. In conclusion, Pte exerts a protective effect against MI/R injury by suppressing oxidative/nitrative stress. These results provide evidence that Pte might be a therapeutic approach for the treatment of MI/R injury.     

Reduction of myocardial damage and polymorphonuclear leukocyte accumulation following coronary artery occlusion and reperfusion by the thromboxane receptor antagonist BM 13.505

This study was designed to assess the effect of the thromboxane receptor antagonist, BM 13.505, in limiting myocardial damage and polymorphonuclear leukocyte accumulation in rats subjected to coronary artery occlusion for 30 min with reperfusion for 24 h (MI/R). Myocardial injury and polymorphonuclear leukocyte infiltration were determined by measuring creatine phosphokinase (CPK) specific activity and myeloperoxidase (MPO) activity, respectively, in the left ventricular free wall (LVFW). Myocardial CPK levels were 8.24 +/- 0.33 U/mg protein in sham MI/R-vehicle-treated animals (n = 18), and were significantly decreased to 6.51 +/- 0.44 U/mg protein in MI/R-vehicle animals (n = 22). Myocardial MPO values were 2.4 +/- 0.5 U/g LVFW in sham MI/R animals, and significantly increased to 10.9 +/- 1.3 U/g LVFW in MI/R-vehicle animals. Administration of BM 13.505 (30 mg/kg, i.p.) 1 min prior to coronary occlusion resulted in CPK values of 7.83 +/- 0.45 U/mg protein and MPO levels of 6.1 +/- 0.9 U/g LVFW (p less than 0.05, compared to the MI/R-vehicle group). The survival rate in the MI/R-BM 13.505 group was 74 and 65% at 2 and 24 h, respectively, and was not different from the MI/R-vehicle group. There were no significant differences in mean arterial blood pressure or heart rate between the MI/R-vehicle and MI/R-BM 13.505 groups, indicating that changes in myocardial oxygen demand do not explain the protective effects. A lower dose did not reduce myocardial injury, indicating that the effects of BM 13.505 were dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS)     

磷酸肌酸联合缺血后适应对大鼠心肌缺血/再灌注损伤的保护作用

目的探讨磷酸肌酸后适应联合缺血后适应对大鼠心肌缺血/再灌注损伤的作用。方法取健康、♂、SPF级Wistar大鼠40只,体质量260～290 g。随机分成4组(各组10只):缺血/再灌注组(I/R组)、缺血后适应组(IPost组)、磷酸肌酸后适应组(PCr组)、磷酸肌酸后适应+缺血后适应组(PCr+IPost组),均给予心肌缺血30 min,再灌注120 min处理。再灌注2 h后用比色法测量各组大鼠血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、髓过氧化物酶(MPO)活性;ELISA方法检测血清肿瘤坏死因子-α(TNF-α);Western blot方法检测缺血心肌磷酸化的蛋白激酶B(P-Akt)、Bcl-2蛋白表达;TTC染色测定心肌梗死面积。结果 IPost、PCr组血清CK、LDH、MPO、TNF-α及心肌梗死面积明显低于I/R组,PCr+IPost组较IPost、PCr组各项指标进一步降低;而IPost、PCr组心肌组织P-Akt、Bcl-2蛋白水平明显高于I/R组,PCr+IPost组较IPost、PCr组蛋白水平进一步升高。结论磷酸肌酸后适应联合缺血后适应可以明显减轻大鼠心肌缺血/再灌注损伤,其作用机制可能与共同激活PI-3K/Akt/Bcl-2信号通路及抑制炎症反应有关。     

Evidence for norepinephrine cardiotoxicity mediated by superoxide anion radicals in isolated rabbit hearts

Catecholamines have been demonstrated to be cardiotoxic. Besides hemodynamic alterations, oxygen free radicals generated by the auto-oxidation of catecholamines might contribute to their deleterious effects. We examined the influence of exogenous norepinephrine (NE), after inhibiting functional alterations by alpha and beta-adrenoceptor blockade, on acute regional ischemia (MI). Method: We used isolated electrically-driven rabbit hearts with depleted catecholamine stores (reserpine 7.0 mg/kg i.p. 16–24 h before preparation, Langendorff, constant pressure: 70 cm H₂O, Tyrode solution, Ca ²⁺ 1.8 mmol/l, 37°C, 185–200 beats/min). Repetitive MI, separated by a reperfusion period of 50 min, was induced by coronary artery branch ligature and quantitated from epicardial NADH-fluorescence photography. Starting after a reperfusion period of 20 min, isolated hearts were treated with NE (10^–6 M), in the presence of propranolol (10^–6 M), phentolamine (10^–6 M) and vitamin C (3 × 10^–8 M) in the perfusion buffer to prevent the functional effects of NE. The influence of the free radical scavenger superoxide dismutase (SOD) (30 U/ml) or captopril (10^–6 M) on MI was also examined. Results: Left ventricular pressure or coronary flow were not significantly affected by either treatment (p>0.05). Epicardial NADH-fluorescence area and intensity were, however, significantly enhanced by NE (+ 22%) (P<0.05), although propranolol, phentolamine and vitamin C had no significant influence on MI (P>0.05). SOD had no significant effect on MI in control hearts (P> 0.05) but completely prevented MI enlargement by NE (P>0.05). Captopril did not significantly affect MI in control hearts and did not inhibit MI enlargement by NE (P<0.05). Conclusion: NE has deleterious effects .on MI in isolated rabbit hearts that are independent of functional alterations. This MI enlargement by NE is mediated by superoxide anion radicals since it could be prevented by SOD. Free radical scavenging properties reported for vitamin C, propranolol or captopril in several in-vitro systems are uneffective in preventing NE cardiotoxicity mediated by oxygen free radicals in isolated rabbit hearts. Correspondence to: A.F.E. Rump at the above address     

Regional and temporal profiles of phorbol 12,13-dibutyrate binding after myocardial infarction in rats: effects of captopril treatment

Phosphoinositide turnover and protein kinase C (PKC) mediate the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). To determine whether PKC is activated after MI, rat hearts after MI were subjected to in vitro quantitative autoradiography with [3H]phorbol 12,13-dibutyrate (PDBu), which is highly selective for PKC. [3H]PDBu binding in the infarcted area increased significantly compared with the non-infarcted region 7 and 21 days after MI, but not 1 and 3 days and 10 months after MI. [3H]PDBu binding in the noninfarcted area was similar to that in the sham-operated rats. Immunohistochemical analysis revealed that abundant macrophages (7 days after MI), fibroblasts, and myofibroblasts (7 and 21 days after MI) occupied the infarcted region. To investigate whether myocardial [3H]PDBu binding is affected by captopril, hearts were subjected to in vitro autoradiography with [3H]PDBu after 1- or 3-week captopril treatment or no treatment. Captopril treatment significantly suppressed [3H]PDBu binding in the infarcted area 3 weeks after MI, but not 1 week after MI nor in the noninfarcted areas. These results suggest that PKC is upregulated during the healing and fibrogenic process after MI and that captopril treatment suppresses the upregulation in the infarcted area.