缺血预处理对肝超微结构的保护作用

我们通过对肝细胞重要超微结构改变进行统计学分析,旨在对ＰＣ在肝脏缺血再灌注损伤中的保护作用作进一步研究。 一、材料与方法 １．动物分组及实验方法：健康成年杂种犬 １８条,体重 ９．５～ １１．５ ｋｇ,采用静脉注射硫贲妥钠 （１５～ ２５ ｍｇ／ｋｇ）后气管插管,控制呼吸,潮气量为１０～１５ ｍｌ／ｋｇ,行左侧股动脉插管测平均动脉压。采用 Ｐｒｉｎｇｌｅ氏法复制肝缺血再灌注犬动物模型进行研究。将１８只犬随机分为三组。Ａ组：非缺血对照组（犬数＝６）,开腹后即取右肝组织标本。Ｂ组：缺血再灌注组（犬数＝６）,游…     

腺苷对缺血预处理心肌的保护作用

腺苷对缺血预处理心肌的保护作用车玉英１综述贾国良２陈士良２审校（１空军西安４５１医院心内科西安７１００５４２第四军医大学西京医院心内科）关键词心肌缺血腺苷多次短暂的缺血发作可以使心肌在随后发生持续性缺血的耐受性增强，这一现象称为缺血预处理(ｉｓｃｈｅ...     

应用S-腺苷蛋氨酸预处理在大鼠肝脏缺血再灌注损伤中的保护作用

目的 研究S-腺苷蛋氨酸预处理对大鼠肝脏缺血再灌注损伤的保护作用及其机制.方法 将54只大鼠随机分为假手术组、缺血再灌注(I/R)组和S-腺苷蛋氨酸预处理(S-arleneyslmethioaine,SAM)组.SAM组大鼠缺血前2 h行腹腔注射SAM预处理.假手术组仅做分离,不阻断肝门;其余两组大鼠均在阻断肝门左、中...     

腺苷预处理和缺血预处理心肌保护效果对比研究

目的探讨心肌腺苷预处理和缺血预处理对离体大鼠心脏缺血/再灌注后心肌功能的影响。方法采用离体大白鼠工作心脏模型,比较腺苷预处理和缺血预处理对心肌缺血再灌前、后左室收缩压(LVSP)、左室舒张末期压(LVDEP)、左心室内压上升及下降最大速率(±dp/dtmax)、主动脉压(AP)、冠脉流量(CF)、心输出量(CO)、每搏心输出量(SV)和冠脉流出液乳酸脱氢酶(LDH),心肌三磷酸腺苷(ATP)含量、超氧化物歧化酶(SOD)活性、脂质过氧化物(LPO)含量及自灌注停搏液至完全停搏的时间(AT)。结果3组大鼠AT间差异有显著性意义(P<0.05),且Control组与其他两组间差异均有显著性意义(P<0.05)。3组大鼠停搏前、复跳后30minAP、LVSP、LVDEP、±dp/dtmax、SV、CF、Co间差异均有显著性意义(P<0.05)。3组大鼠ATP、SOP、LPO、LDH间差异亦均有显著性意义(P<0.05)。结论腺苷预处理和缺血预处理后产生相似的心肌保护作用,明显促进心肌缺血再灌后心肌功能的恢复,增进心脏的收缩功能、心肌ATP含量和SOD活性的恢复,减少LDH的漏出。腺苷预处理对心脏模拟体外循环的缺血再灌注损伤具有保护作用,具有临床应用价值。     

腺苷及缺血后处理对兔缺血再灌注心肌的保护作用

目的 探讨腺苷对缺血再灌注后心肌的保护作用,及其与缺血后处理的关系.方法 40只健康大耳白兔,随机分为对照组、拮抗剂组、缺血后处理组、腺苷治疗组4组,每组10只.制备在体兔心肌缺血再灌注模型,检测心肌收缩功能指标,测量心肌梗死范围,观察缺血再灌注即刻应用腺苷及缺血后处理对兔缺血再灌注后心肌的影响.结果 腺苷治疗组和缺血后处理组与对照组和拮抗剂组相比,再灌注之后左室内压峰值、左室内压最大上升速率和左室内压最大下降速率的恢复率差异有统计学意义(P＜0.05);梗死范围均明显低于对照组和腺苷受体拮抗剂组(P<0.01);心肌酶学LDH和CK含量较对照组和腺苷受体拮抗剂组明显降低(P<0.01).结论 腺苷/腺苷受体途径是缺血后处理的重要途径之一,能够减轻缺血再灌注损伤,保护心肌.     

缺血预处理对糖尿病在体大鼠心肌环磷酸腺苷及环磷酸腺苷依赖蛋白激酶表达的影响

目的 探讨糖尿病大鼠心肌缺血预处理（IPC）后环磷酸腺苷（cAMP）及环磷酸腺苷依赖蛋白激酶（PKA）表达的变化.方法 选取糖尿病与非糖尿病SD大鼠各30只,分为3组（n=10）：假手术（Sham）组,缺血再灌注（I/R）组及IPC组.比较各组血清肌酸激酶（CK）、肌酸激酶同工酶（CK MB）、乳酸脱氢酶（LDH）、心肌梗死面积（MI）及心肌cAMP、PKA含量的变化.电镜标本观察心肌线粒体.结果 非糖尿病大鼠中,IPC组与I/R组比较,CK减少[（2428.32±170.19）vs（6324.06±356.26） U/L,P＜0.05],LDH减少[（1698.98±129.65）vs（4660.15±115.84） U/L,P＜0.05],CK-MB减少[（1450.43±23.56）vs（3280.90±71.33）U/L,P＜0.05],MI减少[（5.63±9.32）％vs（17.75±7.36）％,P＜0.05].糖尿病大鼠中,IPC组与I/R组比较,CK、LDH、CK-MB、MI未见明显缩小[（5962.63±145.22）vs（6012.13±124.08） U/L,（5998.44±123.40）vs（6023.54±89.01）U/L,（4011.13±81.09）vs（4380.71±76.21）U/L,（18.54±2.39）％vs（15.25±4.33）％,P＞0.05].非糖尿病大鼠中,IPC组与I/R组比较,cAMP增加[（0.61±0.07）vs（0.32±0.06） pmol/g,P＜0.05],PKA含量增加[（17.05±1.75）vs（12.68±1.13） pmol/（mg·min）,P＜0.05],糖尿病大鼠IPC组cAMP、PKA含量无明显增加[（0.35±0.04）vs （0.37±0.08） pmol/g,（12.14±2.15）vs（11.79±1.16） pmol/（mg·min）,P＞0.05].非糖尿病大鼠IPC组线粒体的损伤减轻,而糖尿病大鼠IPC组线粒体损伤未见减轻.结论 非糖尿病大鼠IPC可保护心肌.糖尿病抑制IPC的心肌保护作用,其机制可能与糖尿病大鼠心肌cAMP信号系统表达受抑制有关.     

缺血预处理时心肌细胞三磷酸腺苷含量和超微结构变化

采用生物发光技术，分别测定缺血预处理和对照组再灌注60min时心肌细胞三磷酸腺苷（ATP）含量，同时留取心肌标本行光镜和电镜观察，探讨缺血预处理保护心肌的作用机理。结果表明：①缺血预处理组心肌细胞ATP含量明显高于对照组，差异显著（P＜0．05）；②缺血预处理组光镜、电镜所见心肌损伤均明显比对照组轻。提示：缺血预处理可以减少心肌细胞能量消耗，保护线粒体的结构和功能，从而对缺血心肌具有一定保护作用。     

缺血预处理时环磷酸腺苷含量及其依赖蛋白激酶活性的变化

目的:应用大鼠在体缺血/再灌注模型,探讨心肌缺血预处理程序(PC)中环磷酸腺苷(cAMP)含量及cAMP依赖蛋白激酶(PKA)活性的变化及意义。方法:选择36只SD大鼠,进一步分为PC1-、2-、3-(缺血)组和PC1 、2 、3 (再灌注)组。用手术套管法造成左冠状动脉主干缺血及再灌注。损伤后取心脏用放射免疫法测cAMP水平,生化法测PKA活性变化。结果:心肌缺血预处理程序中cAMP含量及PKA活性随缺血及再灌注呈周期性波动。在5min缺血预处理时表现为反复明显增高,而在间隔的再灌注程序中恰呈相反改变,明显下降。再预处理程序中,5min缺血期相对于同一周期中的5min再灌注期,cAMP含量及PKA活性均有显著差异(P<0.01)。结论:cAMP及PKA的周期性波动变化可能是激发心肌缺血预适应(IP)的机制之一,cAMP可能在预处理保护作用中起重要作用。     

Improved functional recovery after ischemic preconditioning in the globally ischemic rabbit heart is not mediated by adenosine A1 receptor activation

Summary Experiments were carried out to test the hypothesis that preconditioning reduces the impairment of recovery of cardiac mechanical function and that this effect is mediated by activation of adenosine A₁ receptors. Isolated hearts were Langendorff-perfused at 37°C with oxygenated blood and paced at 3 Hz. They were divided into 5 groups, all subjected to 45 min global ischemia followed by one hour of reperfusion: 1) Control hearts (n=7) which received no treatment or short ischemia before the long ischemia, 2) preconditioned hearts (n=7), submitted to 5-min zero-flow global ischemia, followed by 5 min reperfusion before the long ischemia, 3) hearts pretreated with sulfophenyltheophylline (SPT 100 M) before preconditioning and long ischemia (n=6), 4) hearts in which preconditioning was substituted by administration of 10 M phenyl-isopropyl-adenosine (PIA) over 5 min, and 5) hearts in which preconditioning was substituted by the administration of 1.5 mg adenosine over 5 min. Hemodynamic results show significant improvement of the postischemic recovery of left ventricular developed pressure (DP) by preconditioning. SPT pretreatment did not reverse the improvement of recovery, obtained by preconditioning, whereas PIA treatment could not mimic preconditioning. Adenosine treatment caused some improvement of recovery of DP, but which remained lower compared to that caused by preconditioning. The contracture developed during ischemia persisted in control hearts, whereas contracture disappeared in non-treated preconditioned hearts. SPT did not prevent the decrease in contracture by preconditioning although values remained slightly higher than in the nontreated preconditioned hearts. PIA did not substitute for preconditioning in preventing contracture. In the adenosine treated group, some decrease of contracture occurred during reperfusion, but values remained significantly higher than in preconditioning.We conclude that receptor A₁ activation is not the main mechanism underlying improved functional recovery conferred by preconditioning since an A₁ receptor blocker (SPT) cannot reverse the effect of preconditioning and an A₁ receptor agonist (PIA) cannot mimic it. Administration of exogenous adenosine reduces functional impairment to a certain extent, but less than preconditioning.     

心肌缺血预处理和腺苷预处理对兔心肌缺血保护作用的比较

目的 :研究缺血预处理与“腺苷预处理 对兔心收缩功能和心肌梗死范围的影响 ,探讨两种处理方法对再灌注损伤的可能有益作用。方法 :采用兔缺血再灌注模型 ,分别以缺血前短暂心肌缺血预处理 ,缺血前腺苷预处理和缺血前应用腺苷受体阻滞剂后行缺血预处理。采用 RM- 6 2 80多道生理纪录和分析处理系统处理心肌收缩功能指标 ,采用 Evans蓝 - TTC法测量心肌梗死范围。结果 :与对照组和腺苷受体拮抗剂组相比 ,缺血预处理组及腺苷预处理组心肌梗死范围均减少 （P<0 .0 1） ;左室内压峰值 （L VSP）恢复率和± dp/ dtmax恢复率均增高 （P<0 .0 5 ） ;心律失常发生率均降低。结论 :缺血预处理与腺苷预处理对缺血心脏具有相似的保护作用 ,可改善缺血 -再灌心脏收缩功能 ,缩小心肌梗死范围     

预处理对在体大鼠心肌细胞的保护作用

目的：探讨缺血预处理对心肌细胞的保护作用。方法：在体大鼠心肌细胞缺血／复灌模型中，观察缺血预处理对心肌细胞再次长时间缺氧／复氧或缺血／复灌损伤的保护作用（LDH释放，MDA，SOD的含量和心肌梗死范围及心律失常等）。结果；在体大鼠心肌缺血预处理组梗死范围和血清LDH较缺血复灌组减少（P＜0．01），预处理组MDA较缺血复灌组也显著降低（P＜0．01）。而且无论是再次的缺血还是复灌期室性心律失常的发生率预处理组明显低于非预处理组（P＜0．01）。结论：缺血预处理可以减少再次长时间的缺血／复灌对心肌的损伤。     

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.     

腺苷介导大鼠心脏缺血后适应的保护效应

目的观察大鼠心肌缺血再灌注时NFκ-B mRNA表达和炎性细胞因子的变化及腺苷后适应对其影响,初步探讨腺苷后适应对缺血再灌注损伤心肌的保护机制。方法健康雄性SD大鼠48只随机分为4组:假手术组、缺血再灌注组、缺血后处理组及腺苷后适应组,每组12只,建立大鼠心肌缺血再灌注模型。光镜下观察心肌组织形态学改变;TTC染色计算各组大鼠心肌梗死面积;RT-PCR检测心肌NF-κB mRNA表达水平,ELISA测定组织中TNF-α及白细胞介素6(IL-6)含量。结果假手术组心肌组织无改变,缺血再灌注组心肌损伤较重,腺苷后适应组及缺血后处理组心肌组织病理学改变明显减轻。与缺血再灌注组比较,腺苷后适应组NF-κB mRNA的表达水平、心肌梗死面积及TNF-α与IL-6的含量明显降低(P<0.01);与缺血后处理组比较,腺苷后适应组NFκ-B mRNA表达及TNF-α、IL-6的分泌均下降(P<0.05)。NFκ-B mRNA的表达与心肌中TNF-α、IL-6浓度呈正相关(P<0.01)。结论腺苷后适应可抑制再灌注后心肌NF-κB的表达活化,从而通过促使炎性细胞因子TNFα-、IL-6分泌减少来减轻缺血再灌注损伤。     

Outcomes and mechanisms of ischemic preconditioning in liver transplantation

BACKGROUND: Liver transplantation is so far the most effective therapeutic modality for end-stage liver diseases, but ischemia/reperfusion (I/R) injury represents a critical barrier to liver transplantation. Primary graft dysfunction and small-for-size syndrome are closely associated with I/R injury. Ischemic preconditioning (IPC) is defined as a brief period of liver ischemia followed by reperfusion, and has demonstrated protections against a prolonged I/R injury and improved the capacity of regeneration. ...     

洛伐他汀预处理的延迟性心肌保护作用及其机制

目的探究洛伐他汀在大鼠心脏急性缺血/再灌注中的延迟性心肌保护作用及其机制。方法SD大鼠24只随机分为3组（每组8只）:模型对照组（C）;Lovastatin组（L）,洛伐他汀直接灌胃两周15mg/（kg·d）;Lovastatin复合LNAME组（N）,洛伐他汀15mg/（kg·d）直接灌胃2周同时腹腔注射LNAME30mg/（kg·d）;2周后建立在体急性缺血/再灌注心脏模型,监测缺血/再灌注前后血流动力学各项指标,同时观察各组血脂水平及其血浆中MDA、SOD、LDH以及CK的变化情况。结果L组和N组较C组心率显著减慢（P<0.01）,缺血/再灌注心律失常消失和再灌注时-dp/dtmax下降显著改善（P<0.05）;各项血脂指标不变的情况下,洛伐他汀显著减少再灌注时血浆中MDA生成和LDH及CK的释放（P<0.01）,并且提高心肌组织SOD活性（P<0.05）。结论Lovastatin对在体大鼠心脏急性缺血/再灌注时具有非降脂外的延迟性心肌保护作用。NO合酶途径是其心脏保护作用的诸多途径之一。     

外源性溶血磷脂酰胆碱和缺血预处理对离体大鼠工作心脏的作用

目的 :观察外源性溶血磷脂酰胆碱 （L PC）对离体大鼠工作心脏的损伤作用及缺血预处理 （IP）对离体大鼠心脏的保护作用。方法 :制备离体大鼠工作心脏模型。随机分为 4组 :C组 :用 K- H液连续灌注 35 min; 组 :停灌注 40 m in,再灌注 30 m in;L 组 :用含 5 μmol/L L PC的 K- H液灌注 5 min,再用正常 K- H液灌注 30 min;P组 :停灌注 5 m in后再灌注 5 min,重复 3次 ,然后重复 L 组全过程。结果 :再灌后 ,L 组和 I组心功能均明显下降 ,室颤发生率提高 ,灌注液中乳酸脱氢酶 （L DH）和丙二醛 （MDA）含量明显升高 ,心肌组织中超氧化物歧化酶 （SOD）活力明显降低。与 L 组相比 ,P组心功能指标明显升高 ,L DH和 MDA含量明显降低 ,SOD活力较高 ,无室颤发生。结论 :L PC可导致与经典方法类似效果的类缺血再灌注损伤作用 ,IP对 L PC损伤有保护作用。     

Post-ischemic intraportal adenosine administration protects against reperfusion injury of canine liver

Although adenosine has been postulated to inhibit ischemia‐reperfusion injury in various tissues, its in vivo cytoprotective mechanism is not fully known. The aim of this study was to determine the effect of intraportally infused adenosine on reperfusion injury in the canine liver. Two h ischemia and reperfusion of the liver were induced in beagle dogs by clamping the portal triad. Either adenosine or saline was infused in the portal vein after reperfusion for 60 min. Levels of serum aspartate aminotransferase and alanine aminotransferase and the survival of animals were examined. Hepatic levels of protein carbonyls and glutathione were also measured, as markers of oxidative stress. One h after reperfusion, the liver was perfused with nitroblue tetrazolium and the formation of formazan was observed to evaluate superoxide formation. Twenty‐four h after reperfusion, 100% of animals in the adenosine group and 33% of animals in the control group survived. Adenosine significantly decreased the reperfusion‐induced increase in serum levels of aspartate aminotransferase and alanine aminotransferase. Adenosine also suppressed the formation of protein carbonyls and the decrease in glutathione levels. Histologically, neutrophil infiltration, superoxide formation, and apoptosis were decreased by adenosine. These results suggest that intraportally infused adenosine attenuates reperfusion injury of the liver, presumably by suppressing the activation of neutrophils and oxidative stress.