远隔预处理和后处理对兔急性心肌缺血再灌注损伤的作用

目的探讨远隔预处理和后处理是否具有减轻兔心肌缺血再灌注损伤的作用及其机制。方法新西兰大白兔40只，随机平均分为4组：对照组、心肌缺血预处理组、肢体缺血预处理组和肢体缺血后处理组，分组进行干预。测定血浆磷酸肌酸激酶（CK）和丙二醛（MDA）活性及心肌梗死面积并检测组织髓过氧化物酶（MPO）活性。结果心肌缺血预处理组、肢体缺血预处理组和肢体缺血后处理组心肌梗死面积、再灌注末MDA活性、缺血组织MPO活性均明显低于对照组（均P〈0．01）。结论远隔预处理和后处理均有显著的心脏保护作用，其作用可能与减轻活性氧的损伤及抗氧化作用加强有关。     

远端缺血预处理心肌保护效应研究进展

远端缺血预处理(RIPC)是通过给予一个器官缺血预处理可以增加远处器官对缺血再灌注损伤的耐受性。基础研究和临床试验均证实RIPC是一项安全有效的干预措施,具有降低心肌缺血再灌注损伤的心肌保护效应。本文就近年来RIPC心肌保护效应和临床应用研究新进展做一综述。     

缺血预处理对大鼠脑缺血再灌注损伤神经细胞的保护作用

目的探讨大鼠局灶性脑缺血预处理对脑缺血再灌注损伤后神经元的保护作用。方法健康雄性SD大鼠60只,随机分为3组:假手术组、大脑中动脉缺血再灌注(MCAO)组、预处理(BIP)组,每组按照再灌注后12 h、1、2、3 d四个时间点平均分为4个亚组,制备缺血预处理模型,分别用流式细胞术和ELISA法观察脑缺血预处理对缺血再灌注大鼠缺血半暗带神经细胞凋亡率及血清神经元特异性烯醇化酶(NSE)含量的影响。结果大鼠脑缺血再灌注后12 h,MCAO组细胞凋亡发生率及血清中NSE的含量较假手术组显著增加(P<0.01),1 d时达到高峰,以后时间点逐渐下降,但仍高于假手术组(P<0.01);BIP组各个时间点神经元凋亡发生率及血清NSE较MCAO组显著降低(P<0.05,P<0.01)。结论大鼠局灶性脑缺血预处理对脑缺血再灌注神经元损伤有保护作用。     

线粒体钙单向转运体在远距预处理脑保护中的作用及其机制

目的探讨肢体缺血预处理（LIP）对脑缺血/再灌注（I/R）损伤保护作用中线粒体钙单向转运体（MCU）的作用及其作用机制。方法将50只I/R损伤模型大鼠随机分为五组。模型组不干预,钌红组、精胺组、LIP组及LIP＋精胺组分别于再灌注前予钌红、精胺、LIP及LIP＋精胺干预。再灌注24 h观察各组神经功能评分,血清丙二醛（MDA）、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）水平及脑皮质区Bcl-2阳性细胞数。结果钌红组及LIP组神经功能评分及血清MDA、LDH水平明显低于另三组,SOD水平及Bcl-2细胞明显高于另三组,P均〈0.05。结论 CIP对I/R的脑保护作用可能与MCU有关;增强MCU活动可抑制LIP的脑保护作用。     

Gentamicin effects on renal ischemia/reperfusion injury.

This study assessed gentamicin's effects on ischemia/reperfusion renal injury to better understand when and how it worsens postischemic acute renal failure. Rats were subjected to 25 minutes of renal pedicle occlusion with and without preischemic (15-minute) or postischemic (15-minute or 8-hour) gentamicin treatment (100 mg/kg, by itself a subtoxic dose). Gentamicin's impact on hypoxia/reoxygenation injury to isolated rat proximal tubular segments was also assessed. Preischemic and postischemic gentamicin worsened the severity of acute renal failure to the same degree, suggesting that pretreatment induces its effect in the reperfusion period. Gentamicin paradoxically lessened hypoxic damage to proximal tubular segments (assessed by lactate dehydrogenase release), again implying no adverse impact on oxygen deprivation-induced tubular injury. From 0-4 hours of reperfusion, gentamicin approximately halved ATP/ADP ratios (due to increased ADP), indicating a drug-induced defect in cellular energetics. This abnormality temporally correlated with evolving morphological damage. Although antioxidants (deferoxamine and sodium benzoate) have been reported to protect against pure aminoglycoside nephrotoxicity, they did not mitigate gentamicin's adverse impact on postischemic acute renal failure. Gentamicin did not influence ischemia/immediate reperfusion deacylation/reacylation (assessed by renal free fatty acid content) despite its known antiphospholipase activity. Although in the normal kidney gentamicin preferentially accumulated in cortex, in the postischemic kidney, both cortex and outer medullary stripe developed striking (approximately threefold to fivefold) and comparable gentamicin increments. In conclusion, gentamicin appears to exacerbate postischemic acute renal failure by adversely influencing the reperfusion, not the ischemic injury, process. This may occur because increased gentamicin accumulation negatively impacts on reperfusion cellular energetics.     

Protective effects of ischemic preconditioning on lung ischemia reperfusion injury: an in-vivo rabbit study

BACKGROUND: The goal of this study was to determine the effect of ischemic preconditioning on the extent of normothermic lung ischemia reperfusion injury in rabbits in vivo. METHODS: Thirty male Japanese white rabbits were randomized into two groups. Fifteen rabbits were treated with ischemic preconditioning (their left lung hilus clamped for 10 minutes and released for 15 minutes (group IP)). Fifteen rabbits were not treated with ischemic preconditioning (group C). Then the left lung hilus of both groups were occluded for 60 minutes and reperfused for 60 minutes. Mean arterial pressure, mean pulmonary artery pressure, and core temperature were recorded. Femoral artery blood samples and lung tissue samples were collected after ischemic preconditioning and after 60 minutes of reperfusion. RESULTS: The lung tissue showed little injury after ischemic preconditioning. After 60 minutes of reperfusion, the angiotensin II (A II) and arterial oxygen tension (PaO2) levels in group IP were significantly higher than those in group C, mean pulmonary artery pressure in group IP was significantly lower than that in group C, the wet/dry ratio and malondialdehyde content of lung tissue in group IP was significantly lower than that in group C, the superoxide dismutase contents of lung tissue in group IP was significantly higher than that in group C, and histological findings showed less damage in group IP than in group C. CONCLUSION: Lung ischemic preconditioning could reduce normothermic rabbit lung ischemia-reperfusion injury. The possible mechanisms are increased production of endogenous A II and reduced formation of oxygen free radicals during lung ischemia for 60 minutes followed by reperfusion for 60 minutes.     

粒细胞集落刺激因子对家兔心肌缺血再灌注损伤的急性保护作用研究

目的 探讨静脉用粒细胞集落刺激因子（granulocyte colony-stimulating factor,G-CSF）对家兔缺血再灌注心肌是否有急性保护作用,既能否增加心肌保护性蛋白磷酸化-丝氨酸/苏氨酸蛋白激酶（ phosphorylation-Akt,p-Akt）的表达及是否具有抑制室性心律失常作用.方法 14只家兔随机平均分为2组（G-CSF组和对照组,n=7）.所有家兔均开胸结扎冠状动脉左前降支30min,再灌注4 h（G-CSF组再灌注同时静脉泵G-CSF 10 μg/kg维持30 min,对照组静脉用生理盐水10 mL/kg维持30 min）.利用60道袜套状电极进行双心室整体心外膜电生理标测.两组分别于基础状态下,缺血时及再灌注4h后通过程序性电刺激诱发心室颤动（VF）,并测定除颤阈值（defibrillation threshold,DFT）.通过快速傅里叶转换技术测定每个标测电极的VF激动频率.应用Curtis-Walker评分系统评价两组再灌注4h内室性心律失常发生情况.ELISA法测定血清肿瘤坏死因子α（TNF-α）和白细胞介素-10（IL-10）的浓度,蛋白质印迹（Western Blot）测定缺血区心肌p-Akt的表达水平.结果 所有家兔均可通过程序性电刺激诱发出稳定VF.与对照组相比,G-CSF显著降低了再灌注室性心律失常分数[（6.3±1.5）对（2.3±2.6）,P=0.038].两组间基础状态下、缺血及再灌注时DFT及VF激动频率差异无统计学意义（P＞0.05）.两组再灌注4h后VF激动频率较基础状态及缺血时降低,差异有统计学意义（P＜0.05）.G-CSF不增加血清TNF-α及IL-10的浓度,但可增加缺血区心肌P-Akt的表达.结论 静脉用G-CSF未改变VF激动频率及缺血再灌注DFT,但是G-CSF通过增加缺血区心肌组织中p-Akt的表达可减少心肌损伤,减少再灌注心律失常.研究结果提示静脉使用G-CSF对缺血再灌注心肌具有一定的急性保护作用.     

Paclitaxel enhances the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged rat

正Objective To investigate if paclitaxel can enhance the protective effect of myocardial ischemia preconditioning on ischemia/reperfusion injury in aged rat and explore related mechanism. Methods Primary cardiomyocytes of Sprague-Dawley rats were isolated by trypsin and divided into 5 groups (n=6 each):control group,hypoxia injury group,hypoxia preconditioning group,paclitaxel group,and paclitaxel+hypoxia preconditioning     

三碘甲状腺原氨酸和缺血预适应对大鼠小肠缺血再灌注损伤的作用

目的了解缺血预适应和Ｔ３对小肠缺血再灌注损伤的作用。方法观察缺血预适应和Ｔ３对大鼠小肠缺血再灌注后肠组织腺苷酸含量和肠粘膜损伤的影响。结果Ｔ３组和预适应组（预适应为１０分钟缺血后１５分钟再灌注）的小肠组织ＡＴＰ及总腺苷酸含量均明显高于对照组（Ｐ＜０．０５）,肠粘膜损伤亦明显减轻;且Ｔ３组比预适应组肠粘膜损伤更轻（Ｐ＜０．０５）,动物存活率增加（Ｐ＜０．０５）。结论Ｔ３和缺血预适应对小肠缺血再灌注损伤有一定保护作用,且Ｔ３效果更佳。     

大鼠肝脏缺血再灌注损伤c-fos表达及预处理的保护作用

目的探讨预处理（preconditioningPc）对大鼠肝脏缺血再灌注（ischemia／reperfusion,I／R）损伤的影响及其机制。方法制备大鼠肝脏原位I／R损伤的模型,采用免疫组织化学技术结合图像分析方法定量检测原癌基因c-fos表达的情况和肝组织脂质过氧化产物丙二醛（MDA）的变化。结果I／R损伤早期可引起损伤区肝细胞核内原癌基因c－fos的大量表达;PC明显减少了c－fos表达的细胞数量以及减轻肝脏脂质过氧化的程度。结论PC对大鼠肝脏I／R损伤有明显的保护作用,可能的机制之一是抑制肝I／R损伤后原癌基因c-fos的表达和灭活自由基减少脂质过氧化物的生成。     

Antioxidant and cardioprotective effects of N-tyrosol in myocardial ischemia with reperfusion in rats

We demonstrated in experiments on rats with left coronary artery occlusion that intravenous administration of 20 mg/kg n-tyrosol during ischemia limited manifestations of oxidative stress in myocardial tissue during early post reperfusion period: content of diene and triene conjugates lowered 16 and 20%, respectively. This was associated with higher preservation of cardiomyocytes and reduction of the infarction zone.     

异氟烷预处理对离体大鼠心肌缺血再灌注损伤的影响

目的:采用Langendorff离体心脏灌注模型,研究异氟烷预处理对离体大鼠心肌缺血再灌注损伤的影响。方法:24只SD大鼠随机分为4组,每组6只,分别为缺血再灌注损伤组(IR组)、异氟烷预处理1组(IsoP 1组)、异氟烷预处理2组(IsoP 2组)和异氟烷预处理3组(IsoP 3组)。监测复灌后心功能恢复情况、冠脉流出液中磷酸肌酸激酶(CK)、乳酸脱氨酶(LDH)的释放量和心肌存活面积的变化。结果:复灌期间3组IsoP心脏各对应时间点的LVEDP均显著低于对照组(P<0.05~<0.01);再灌注30 min时IsoP各组LVDP的恢复均高于IR组(P<0.05),IsoP3组±dp／dtmax在再灌注30 min时的恢复百分比均高于IR组(P<0.05),IsoP1组+dp／dt max高于IR组(P<0.05);复灌后异氟烷预处理组各时间点的CK、LDH释放量均低于IR组(P<0.01);IsoP2组、IsoP1组和IsoP3组心肌存活面积百分比均高于IR组(P<0.01);预处理各组之间比较无显著性差异(P>0.05)。结论:IsoP对大鼠离体缺血再灌注心肌有保护作用,可以显著减轻心肌细胞的损伤,改善心功能,增加心肌存活面积。     

Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury

Background:

Liver transplantation involves a period of ischemia and reperfusion to the graft which leads to primary non-function and dysfunction of the liver in 5–10% of cases. Remote ischemic preconditioning (RIPC) has been shown to reduce ischemia reperfusion injury (IRI) injury to the liver and increase hepatic blood flow. We hypothesized that RIPC may directly modulate hepatic microcirculation and have investigated this using intravital microscopy.

Methods:

A rat model of liver IRI was used with 45 min of partial hepatic ischemia (70%) followed by 3 h of reperfusion. Four groups of animals (Sham, IRI, RIPC+IRI, RIPC+Sham) were studied (n= 6, each group). Intravital microscopy was used to measure red blood cell (RBC) velocity, sinusoidal perfusion, sinusoidal flow and sinusoidal diameter. Neutrophil adhesion was assessed by rhodamine labeling of neutrophils and cell death using propidium iodide.

Results:

RIPC reduced the effects of IRI by significantly increasing red blood cell velocity, sinusoidal flow and sinusoidal perfusion along with decreased neutrophil adhesion and cell death.

Conclusions:

Using intravital microscopy, this study demonstrates that RIPC modulates hepatic microcirculation to reduce the effects of IRI. HO-1 may have a key role in the modulation of hepatic microcirculation and endothelial function.     

异氟醚预处理对心肌缺血再灌注损伤的保护作用

目的:观察异氟醚预处理对体外循环心内直视手术心肌的保护作用。方法:20例瓣膜置换术患者(ASA 2～3 级),随机分为预处理组(Ⅰ组)和对照组(C组)。分别于麻醉后(T_1),主动脉开放后15分钟(T_2)、2小时(T_3)、24小时(T_4)时间点取血样,检测血清CGRP、ET、cTnI;另于术前、术后第1、3天记录同步12导联心电图.测定其QTd和 QTcd。结果:主动脉开放后,CGRP含量在两组患者24小时之内都有显著增加(P<0.01),T_2时,预处理组的CGRP水平明显高于对照组的(P<0.05);ET在T_2时两组都有显著上升(P<0.01),但预处理组的上升幅度明显低于对照组(P<0.05);T3、T4时,对照组cTnI水平显著高于预处理组;术后两组QTd和 QTcd显著增加(P<0.01),其中对照组的增加较多,且第1天明显多于预处理组(P<0.05);结论:异氟醚预处理能减少心肌的缺血再灌注损伤,降低术后心律失常发生率,有利体外循环后心功能恢复。     

远程缺血后适应对大鼠脑缺血-再灌注损伤的影响

目的探讨远程缺血后适应对大鼠脑缺血-再灌注损伤的保护作用及对内质网应激诱导的凋亡蛋白C／EBP同源蛋白（CHOP）的影响。方法将56只雄性SD大鼠,随机分为假手术组,单纯缺皿组,插栓即刻行缺血后适应组（后适应1组）,再灌注即刻行缺血后适应组（后适应2组）,每组14只。线栓法制作大鼠大脑中动脉缺血2h模型。远程缺血后适应的实行：在插栓后即刻（后适应1组）及再灌注即刻（后适应2组）夹闭双侧股动脉10min,放开10min,此为一次缺血后适应,共进行3次。于再灌注后24h处死大鼠,测定脑梗死体积;免疫组化测定脑组织皮质和基底核CHOP的表达。结果①假手术组大鼠脑组织未见梗死灶,单纯缺血组、后适应1组、后适应2组脑梗死体积百分比分别为（48±10）％、（22±11）％及（26±12）％。与单纯缺血组比较,两缺血后适应组的梗死灶体积均明显减小,差异有统计学意义（P〈0．01）;两缺血后适应组间差异无统计学意义。②在皮质和基底核区,假手术组仅见少量的CHOP阳性表达细胞,单纯缺血组阳性表达细胞明显增多（P〈0．05）;而两后适应组CHOP阳性表达细胞明显减少,与单纯缺血组比较,差异均有统计学意义（P〈0．05）。两缺血后适应组间比较,差异无统计学意义。结论远程缺血后适应对大鼠脑缺血有保护作用。其保护作用可能与减少脑组织中CHOP含量有关。