缺血后处理的心肌保护作用及机制研究进展

近年来,关于缺血后处理心肌保护作用及机制的研究不断深入,在临床实验中提出了药物性缺血后处理和远程组织缺血后处理的概念,这些方法在防治心肌缺血/再灌注损伤中具有显著的保护作用和重要的应用价值,有些已在临床中被证明,但其作用机制复杂,许多细节尚不清楚,本文对近年来国内外有关远程组织缺血后处理心肌保护的机制简要综述。     

联合应用远程缺血后处理和药物性缺血后处理的脑保护作用研究现状

近年来,随着对缺血后处理神经保护作用的研究不断深入,更多的人认识到多种缺血后处理方法的联合应用为卒中患者的治疗带来新的曙光。一些关于多种缺血后处理联合应用的动物实验数据表明,多种缺血后处理的联合应用较之单一的缺血后处理更为有效。本文就目前联合应用远程缺血后处理和药物性缺血后处理的脑保护作用的研究现状进行了综述。     

缺血后处理的心肌保护机制及应用进展

在体外循环心脏手术、冠心病血运重建等心脏病治疗过程中常常发生心肌缺血再灌注损伤（myocardial ischemia/reperfusion injury,MIRI）,影响治疗效果.MIRI是由多种触发物、媒介物和效应器参与的复杂生物反应过程,导致炎性反应、内皮细胞损伤和心肌细胞凋亡.     

IGF-1后处理与缺血后处理对缺血再灌注心肌保护作用的对比研究

目的 比较胰岛素样生长因子-1后处理(IGF-1-POST)与缺血后处理(I-POST)对缺血再灌注心肌的保护作用,探讨两者抑制缺血再灌注心肌凋亡的可能机制.方法 采用垫扎球囊法建立模型,将48只SD大鼠随机均分成4组(n=12):假手术组、I/R组、I-POST组、IGF-1-POST组.除假手术组外其余各组均缺血4...     

缺血后处理对大鼠肠缺血再灌注保护作用及机制

 目的 观察肠缺血后处理(I-post C)对缺血再灌注(IR)损伤的保护作用,探讨I-postC在肠IR损伤中的作用机制.方法 雄性SD大鼠72只,随机分为假手术组(S组),缺血再灌注组(IR组)和缺血后处理组(I-postC组),每组再分为再灌注10 min、45 min及90 min三亚组,测定血浆及肠组织二氨氧化酶(DAO)活性、超氧化物歧化酶(SOD)活性、丙二醛(MDA)浓度、髓过氧化酶(MPO)含量、诱导型一氧化氮合成酶(iNOS)mRNA表达量,以及血浆一氧化氮(NO)浓度 (以NO2-/ NO3-代表).结果 (1)与IR组比较,I-postC组肠组织DAO在45 min和90min显著升高(P<0.05),血浆DAO在45 min和90 min显著减低(P<0.05);(2)与IR组比较,I-postC组在10、45和90 min降低肠组织MDA与MPO含量(P<0.05),在45 min与90 min显著升高肠组织SOD活性(P<0.05);(3)I-postC组血浆NO含量及iNOS mRNA表达在45 min和90 min均明显高于IR组(P<0.05).结论 肠IR损伤与iNOS过高表达及NO大量产生有关.I-postC对肠IR损伤的拮抗作用可能与I-postC诱导早期产生低水平NO,发挥其信号保护效应相关.     

远程缺血预处理对心肌保护的研究进展

近年来,随着远程缺血预处理(remote ischemic preconditioning,RIPC)的心肌保护作用及机制研究的不断深入,RIPC对心肌保护作用的临床意义也逐渐受到重视。为此,作者就RIPC对心肌保护作用及其可能的机制研究进展作一综述。     

缺血后处理对缺血再灌注损伤肾脏保护的研究进展

肾移植、肾切开取石术、肾部分切除术等复杂手术和血管外科的主动脉修补术等,术中阻断肾脏血流会引起肾缺血再灌注损伤（ischemia reperfusion injury,IRI）;休克后微循环再通、体外震波碎石也会引起肾IRI,成为影响术后患者康复及生存率的重要因素。     

去铁敏对心肌的保护作用

去铁敏（Desferrioxamine mesylate,DFO）是从链球菌中提取的一种铁载体,为高选择性的铁螯合剂。它对Fe2＋亲和力较低,对Fe3＋的亲和力极高（Kd=1031）,是铜亲和常数的107倍,而对钙的亲和力可忽略不计（Kd=102）,还可与镓、铝等金属离子结合。去铁敏主要与Fe3＋以l：l比例结合形成铁胺复合物,     

氧化应激在大鼠肢体缺血/再灌注心肌损伤中的作用

目的观察大鼠肢体缺血／再灌注（LIR）后心肌组织的损伤性变化并探讨氧化应激在其发生机制中的作用。方法用健康雄性Wistar大鼠制备LIR动物模型，采用生物化学方法及比色法测定心肌组织丙二醛（MDA）、髓过氧化物酶（MPO）、ATP、乳酸（LD）含量及ATP酶（ATPase）活性；测定血浆肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）水平，光镜观察心肌组织的形态学变化。结果与对照组比较，再灌注后心肌组织ATP储备减少，LD含量增加，各型ATPase活性下降，血浆CK、CK-MB及心肌组织MDA、MPO含量均增高（P〈0．05或P〈0．01）。镜下可见再灌注后心肌组织炎性细胞浸润，部分心肌横纹不清晰，少数心肌细胞变性。结论LIR可对心肌组织造成一定损伤，这与体内的氧化应激状态有密切关系。     

辛伐他汀预处理减轻缺血再灌注心肌损伤的实验研究

目的 研究辛伐他汀预处理对大鼠缺血再灌注心肌损伤的保护作用并探讨相关机制.方法 通过冠状动脉结扎法建立大鼠心肌缺血再灌注模型.实验动物分为假手术组、对照组和辛伐他汀组.辛伐他汀组按照5 mg/(kg·d)的剂量术前7 d起灌胃.观察各组室性心律失常发生率及心肌细胞超微结构变化,测定梗死心肌面积,检测血清心肌酶谱、脂质水平及心肌肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和单核细胞趋化因子(MCP)-1的含量.结果 与对照组相比,辛伐他汀预处理可以:(1)显著降低心律失常评分;(2)显著下调血清磷酸肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)水平;(3)减少再灌注后心肌梗死区面积/缺血危险区面积比;(4)保护再灌注心肌细胞超微结构.各组血清总胆固醇、三酰甘油、低密度脂蛋白、高密度脂蛋白未见差异,辛伐他汀组心肌组织TNF-α、IL-6和MCP-1含量与对照组比较差异有统计学意义(P<0.01).结论 辛伐他汀预处理能减轻大鼠心肌缺血再灌注损伤,这种作用不依赖于其降脂作用,可能与其降低再灌注心肌炎性细胞因子表达相关.     

血小板激活因子拮抗剂SRI63-441对缺血再灌注损伤大鼠心肌的保护作用

目的 :研究血小板激活因子拮抗剂SRI6 3 - 44 1对大鼠缺血再灌注损伤心肌的保护作用。方法 :将实验大鼠分成 3组 ,对照组未行缺血及药物治疗 ,再灌注组及SRI6 3- 44 1治疗组结扎大鼠左冠状动脉前降支 (LAD)缺血 30min后 ,行再灌注 10h ,其中治疗组结扎前 1min给予SRI6 3 - 44 1(1mg/kg) ,观察大鼠再灌注心律失常 ,再灌注区心肌组织中丙二醛浓度、超氧化物歧化酶活性的变化。结果 :SRI6 3- 44 1能明显降低再灌注时室性心律失常的严重程度 ,使缺血 30min再灌注 10h大鼠的心肌梗塞面积从 (2 1 6± 3 1) %降至 (12 7± 2 5 ) % ,心肌组织中脂质过氧化最终产物丙二醛 (MDA)含量下降 ,超氧化物歧化酶 (SOD)活性升高。结论 :SRI6 3 - 44 1用于大鼠心肌缺血再灌注可减少心肌损伤 ,揭示PAF为心肌再灌注损伤的重要介质 ,而PAF拮抗剂有可能用于心肌缺血再灌注损伤的治疗。     

异氟醚心肌保护作用机制与临床应用

越来越多的基础与临床研究证明异氟醚能明显减轻心肌缺血／再灌注损伤,这种保护作用主要以异氟醚缺血再灌注后预处理和后处理的方式实现。其作用机制目前有多种学说,其中包括：触发体内多种介质相互作用,激活多条信号传导系统如蛋白激酶（PKC）通路、酪氮酸蛋白激酶（PTK）通路和有丝分裂原激活蛋白激酶（MAPKs）通路等,使细胞产生多种保护性效应子如激活腺苷受体、开放线粒体膜表面ATP敏感钾通道、降低细胞内Ca^2＋超载、增强心肌ATP合成能力与储存、抑制氧自由基堆积、增加BCL-2表达、抑制炎性因子的释放等。研究还表明异氟醚吸入后的心肌保护作用具有一定的临床应用前景。     

辛伐他汀预处理减轻缺血再灌注心肌损伤的实验研究

Objective To investigate the effects of pretreatment with simvastatin on iscbemia reperfusion induced myocardial injury, and to further explore related mechanism with respect to inflammation modulation. Methods The rat myocardial ischemia reperfusion model was established by the method of coronary artery ligation. The animals were divided into 3 groups: the sham group, the control group and the simvastatin group. In the simvastatin group, the animals were pretreated with simvastatin (5 mg/kg) one week before by intragastric administration. Ventricular arrhythmia was monitored and scored, infarct size and area at risk of myocardium were determined, and uhrastructural changes were observed. The serum levels of myocardial enzymes and lipids were measured. The content of myocardial inflammatory cytokines [tumor necrosis factor (TNF) -α、interleukin(IL) -6, and monocyte chemoattractant protein(MCP) - 1]were also evaluated. Results When compared with those of the control group, the amount and duration of ventricular arrhythmia in simvastatin group were less and score of ventricular arrhythmia was significantly lower. When pretreated with simvastatin, the serum levels of CK-MB and LDH in simvastatin group were significantly lower than those of the control group. The infarct size/area at risk ratio of the simvastatin treated group was significantly less than those of the control group. The uhrastructures of myocardial cells were better maintained in simvastatin group. No significant differences were observed in the serum concentrations of total cholesterol, triglycerides, low density lipoprotein and high density lipoprotein when comparisons were made each other among the three groups. However, the levels of TNF-α,IL-6 and MCP-1 in heart tissue of the treated animals were significantly lower than those of the control group. Conclusions Pretreatment with simvastatin ameliorates ischemia reperfusion induced myocardial injury, which is partly related with the down-regulation of inflammatory cytokines expression in heart tissue but independent of its role of lipids modulation.     

辛伐他汀预处理减轻缺血再灌注心肌损伤的实验研究

Objective To investigate the effects of pretreatment with simvastatin on iscbemia reperfusion induced myocardial injury, and to further explore related mechanism with respect to inflammation modulation. Methods The rat myocardial ischemia reperfusion model was established by the method of coronary artery ligation. The animals were divided into 3 groups: the sham group, the control group and the simvastatin group. In the simvastatin group, the animals were pretreated with simvastatin (5 mg/kg) one week before by intragastric administration. Ventricular arrhythmia was monitored and scored, infarct size and area at risk of myocardium were determined, and uhrastructural changes were observed. The serum levels of myocardial enzymes and lipids were measured. The content of myocardial inflammatory cytokines [tumor necrosis factor (TNF) -α、interleukin(IL) -6, and monocyte chemoattractant protein(MCP) - 1]were also evaluated. Results When compared with those of the control group, the amount and duration of ventricular arrhythmia in simvastatin group were less and score of ventricular arrhythmia was significantly lower. When pretreated with simvastatin, the serum levels of CK-MB and LDH in simvastatin group were significantly lower than those of the control group. The infarct size/area at risk ratio of the simvastatin treated group was significantly less than those of the control group. The uhrastructures of myocardial cells were better maintained in simvastatin group. No significant differences were observed in the serum concentrations of total cholesterol, triglycerides, low density lipoprotein and high density lipoprotein when comparisons were made each other among the three groups. However, the levels of TNF-α,IL-6 and MCP-1 in heart tissue of the treated animals were significantly lower than those of the control group. Conclusions Pretreatment with simvastatin ameliorates ischemia reperfusion induced myocardial injury, which is partly related with the down-regulation of inflammatory cytokines expression in heart tissue but independent of its role of lipids modulation.     

不同缺血预处理对兔心肌保护作用的实验研究

 目的研究单次和3次缺血预处理对再灌注兔心肌梗塞范围和心肌收缩功能的影响.方法采用在体兔心肌缺血再灌注模型,用RM-6280多道生理记录和分析处理系统处理心肌收缩功能指标,Evans蓝-TTC法测量心肌梗塞范围.结果与对照组相比,不同缺血预处理组心肌梗塞面积均明显减少(P＜0.01);左室内压峰值(LVSP)恢复率和+dp/dtmax恢复率均明显增高(P＜0.05);心律失常发生率均降低,且两预处理组间无显著差异.结论不同缺血预处理对再灌注心脏具有类似的保护作用.     

缺血预处理减轻缺血再灌注损伤作用机制的研究进展

缺血再灌注损伤（ischemia-reperfusion injury，I／R损伤）是一个十分常见的病理过程，在血管外科、骨科及心胸外科都会经常发生，针对I／R损伤，人们探索了不同的减轻损伤的方法，如使用氧自由基清除剂、白细胞清除剂、低温麻醉和控制性再灌注等。Mully等1986年在实验中使犬心缺血5min再灌注5min，共四个周期，再持续缺血40min后再灌注，发现这样处理后心肌梗死面积比对照组减少了70％，他将这种现象定义为“缺血预处理（ischemia preconditioning，IP）”。此后，IP效应在不同的动物以及不同的组织器官中都得到了证实。现将近年来IP减轻组织器官I／R损伤的作用机制研究进展作一综述。     

缺血后处理对局灶性脑缺血再灌注大鼠SOD、MDA的影响

目的：观察缺血后处理对局灶性脑缺血再灌注大鼠SOD、MDA的影响。方法：线栓法建立大鼠大脑中动脉缺血再灌注模型,将成年雄性Wistar大鼠144只,随机分成三组：假手术组、对照组（脑缺血再灌注组）、缺血后处理组？假手术组只进行假手术;对照组（脑缺血再灌注组）给予90min大脑中动脉缺血（MCAO）;缺血后处理组在大脑中动脉缺血90rain后,给予灌注30s缺血30s,反复3次。各组分别再灌注1211、24h、48h、72h后测定脑组织超氧化物歧化酶（SOD）、丙二醛（MDA）水平的改变：结果：局灶性脑缺血后再灌注前给予后处理,缺血后处理组与缺血再灌注组相比,SOD的表达明显增加,而MDA的表达明显减少。结论：脑缺血后处理增加脑缺血再灌注后SOD的表达、减少MDA的表达,进而提高脑组织的抗氧化能力。