Does nitric oxide generation contribute to the mechanism of remote ischemic preconditioning?

The protective effect of local or remote ischemic preconditioning (IPC) on subsequent 40-min ischemic and 120-min reperfusion myocardial damage was investigated. Preconditioned rats underwent one cycle of myocardial ischemia/reperfusion consisting of 5-min ischemia produced as a left coronary artery (LCA) occlusion and 5 min of reperfusion. Remote IPC was produced as 15 min of small intestinal ischemia with 15 min of reperfusion as well as 30 min of limb ischemia with 15 min of reperfusion. A marked protective action was afforded by both IPC protocols with a more significant effect of local (classic) ischemic preconditioning. Since the protective effect of remote IPC was not abolished by nitric oxide (NO) synthase inhibition with Nω-nitro- -arginine ( -NNA) it is concluded that NO generation may not be involved in the mechanism of remote IPC.     

The role of oxygen free radicals in the mechanisms of local and distant ischemic myocardial preconditioning

The phenomenon of ischemic preconditioning consists in increase in myocardial tolerance to ischemia after short periods of ischemia and reperfusion of the myocardium (local preconditioning) or a distant organ (distant preconditioning). This study is dedicated to the role of oxygen free radicals (OFR) in the mechanisms of preconditioning; pharmacological inhibition of OFR with N-2-mercaptopropionylglycin, a synthetic anti-oxidant, was used. Mouse experiments demonstrated a reduction in the infarction-limiting effect of local preconditioning as a result of OFR inhibiting. This confirms the hypothesis according to which OFR play an important role in the mechanisms of launching and mediating the protective effect of local preconditioning. On the contrary, application of the same dose of N2-mercaptopropionylglycin does not lead to a significant weakening of the infarction-limiting effect of distant preconditioning caused by 20 min of ischemia and 15 min of reperfusion of the small intestine. Thus, it is unlikely that OFR participate in the realization of the effect of distant preconditioning caused by small intestinal ischemia. The authors discuss hypothetic molecular mechanisms of distant myocardial preconditioning.     

Evaluation of the effects of ischemic preconditioning on the hematological parameters of rats subjected to intestinal ischemia and reperfusion

OBJECTIVES:

Intestinal ischemia/reperfusion often leads to acute lung injury and multiple organ failure. Ischemic preconditioning is protective in nature and reduces tissue injuries in animal and human models. Although hematimetric parameters are widely used as diagnostic tools, there is no report of the influence of intestinal ischemia/reperfusion and ischemic preconditioning on such parameters. We evaluated the hematological changes during ischemia/reperfusion and preconditioning in rats.

METHODS:

Forty healthy rats were divided into four groups: control, laparotomy, intestinal ischemia/reperfusion and ischemic preconditioning. The intestinal ischemia/reperfusion group received 45 min of superior mesenteric artery occlusion, while the ischemic preconditioning group received 10 min of short ischemia and reperfusion before 45 min of prolonged occlusion. A cell counter was used to analyze blood obtained from rats before and after the surgical procedures and the hematological results were compared among the groups.

RESULTS:

The results showed significant differences in hematimetric parameters among the groups. The parameters that showed significant differences included lymphocyte, white blood cells and granulocyte counts; hematocrit; mean corpuscular hemoglobin concentration; red cell deviation width; platelet count; mean platelet volume; plateletcrit and platelet distribution width.

CONCLUSION:

The most remarkable parameters were those related to leukocytes and platelets. Some of the data, including the lymphocyte and granulocytes counts, suggest that ischemic preconditioning attenuates the effect of intestinal ischemia/reperfusion on circulating blood cells. Our work contributes to a better understanding of the hematological responses after intestinal ischemia/reperfusion and IPC, and the present findings may also be used as predictive values.     

Ischemic Preconditioning of the Rat Brain as a Method of Endothelial Protection from Ischemic/Repercussion Injury

The studies reported here addressed the endothelium-protecting action of local and remote ischemic preconditioning of the brain in rats. Cerebral ischemia lasting 30 min was reproduced by thermocoagulation of the vertebral arteries with simultaneous clamping of the carotid arteries, the procedure being followed by reperfusion via the carotid arteries for 120 min (controls). The early and late phases of ischemic preconditioning and remote preconditioning were reproduced. Brain blood flow was recorded using high-frequency Doppler ultrasonography. The early and late phases of local ischemic preconditioning and the late phase of remote ischemic preconditioning were found to have endothelium-protecting actions apparent as improvements in the recovery of brain blood flow in the post-ischemic period in preconditioned rats, with lower levels of endothelial desquamation and cerebral edema. Blockade of nitric oxide synthesis eliminated the protective effects of both phases of preconditioning.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 90, No. 1, pp. 40–48, January, 2004     

低浓度11,12-EET预干预对大鼠心肌缺血/再灌注损伤的影响

目的:观察外源性低浓度 11,12-EET预干预对大鼠在体心肌缺血/再灌注损伤的影响。方法:雄性Wistar大鼠,开胸,结扎和松开冠状动脉左前降支,复制心肌缺血/再灌注模型;采用缺血 5min/再灌注 5min两次造成缺血预处置。实验分 3组:对照组;缺血预处置组;外源性 11,12-EET预干预组。每组再分为A、B 2小组:A组动物心肌缺血 10min/再灌注 10min,主要观察缺血/再灌注各时程之心律失常;B组动物缺血 6 0min/再灌注 30min,主要观察缺血期心律失常、心功能的变化及再灌注后心肌梗死范围。结果:缺血预处置和 11,12-EET(6 2 4× 10^-8mol/L)预干预均可减轻缺血/再灌注心律失常及心功能的变化,降低心肌梗死范围。结论:11,12-EET预干预具有类缺血预处置样的心肌保护作用.     

Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage in hamster cheek pouch microcirculation

OBJECTIVE:

Ischemic preconditioning and some drugs can protect tissues from injury by preserving microcirculation. This study evaluated vascular permeability in a hamster cheek pouch preparation using either short ischemic periods or bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion.

METHOD:

Sixty-six male hamsters were divided into 11 groups: five combinations of different ischemic frequencies and durations (one, three or five shorts periods of ischemia, separated by one or five minutes) with 10 min intervals between the ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min ischemic periods with 10 min intervals between them followed by the topical application of histamine (2 µM); bradykinin (400 nM) followed by 30 min of ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or histamine or bradykinin by themselves). Macromolecular permeability was assessed by injection of fluorescein-labeled dextran (FITC-dextran, MW = 150 kDa; 250 mg/Kg body weight), and the number of leaks/cm2 was counted using an intravital microscope and fluorescent light in the cheek pouch.

RESULTS:

Plasma leakage (number of leaks/cm²) was significantly reduced by preconditioning with three and five 1 min ischemic periods, one and three 5 min ischemic periods and by bradykinin. Histamine-induced macromolecular permeability was also reduced after three periods of 5 min of ischemia.

CONCLUSION:

Short ischemic periods and bradykinin can function as preconditioning stimuli of the ischemia/reperfusion response in the hamster cheek pouch microcirculation. Short ischemic periods also reduced histamine-induced macromolecular permeability.     

大鼠小肠缺血预适应对缺血-再灌注损伤保护作用及机制

目的:探讨小肠缺血预适应(ischemic preconditioning,IP)对缺血再灌注(ischemia／reperfusion,I／R)肠黏膜损伤的保护作用及可能机制。方法:以大鼠肠系膜前动脉制造I／R和IP模型;用分光光度法测血和肠组织二胺氧化酶(diamine oxidase,DAO)活性;用H-E和PAS特染显示肠黏膜的病理改变并进行Chiu CJ评分;用免疫组化方法显示肠绒毛CGRP、NPY肽能神经并用测微尺测定阳性神经纤维密度。结果:与对照组相比,I／R组及IP I／R组血DAO水平升高而肠黏膜DAO水平降低,肠黏膜损伤Chiu CJ评分数升高;肠绒毛CGRP阳性神经纤维密度降低而NPY阳性神经纤维密度升高;但IP轻于I／R的变化。结论:小肠IP能减轻I／R引起的肠黏膜机械屏障的组织病理损伤,其机制是通过肠黏膜局部CGRP、NPY肽能神经参与调节其微血管舒缩平衡而实现的。     

Remote preconditioning,perconditioning, and postconditioning: a comparative study of their cardioprotective properties in rat models

OBJECTIVE:

Ischemia reperfusion injury is partly responsible for the high mortality associated with induced myocardial injury and the reduction in the full benefit of myocardial reperfusion. Remote ischemic preconditioning, perconditioning, and postconditioning have all been shown to be cardioprotective. However, it is still unknown which one is the most beneficial. To examine this issue, we used adult male Wistar rat ischemia reperfusion models to compare the cardioprotective effect of these three approaches applied on double-sided hind limbs.

METHODS:

The rats were randomly distributed to the following five groups: sham, ischemia reperfusion, remote preconditioning, remote perconditioning, and remote post-conditioning. The ischemia/reperfusion model was established by sternotomy followed by a 30-min ligation of the left coronary artery and a subsequent 3-h reperfusion. Remote conditioning was induced with three 5-min ischemia/5-min reperfusion cycles of the double-sided hind limbs using a tourniquet.

RESULTS:

A lower early reperfusion arrhythmia score (1.50±0.97) was found in the rats treated with remote perconditioning compared to those in the ischemia reperfusion group (2.33±0.71). Meanwhile, reduced infarct size was also observed (15.27±5.19% in remote perconditioning, 14.53±3.45% in remote preconditioning, and 19.84±5.85% in remote post-conditioning vs. 34.47±7.13% in ischemia reperfusion, p<0.05), as well as higher expression levels of the apoptosis-relevant protein Bcl-2/Bax following global (ischemia/reperfusion) injury in in vivo rat heart models (1.255±0.053 in remote perconditioning, 1.463±0.290 in remote preconditioning, and 1.461±0.541 in remote post-conditioning vs. 1.003±0.159 in ischemia reperfusion, p<0.05).

CONCLUSION:

Three remote conditioning strategies implemented with episodes of double-sided hind limb ischemia/reperfusion have similar therapeutic potential for cardiac ischemia/reperfusion injury, and remote perconditioning has a greater ability to prevent reperfusion arrhythmia.     

NO参与缺血预处理对大鼠骨骼肌缺血再灌注损伤的保护作用

目的研究缺血预处理(IPC)对大鼠骨骼肌缺血再灌注损伤的保护作用及一氧化氮(NO)是否参与此保护作用。方法采用Wistar雌性大鼠,在左后肢跟部止血,同时使用血流监测仪测股四头肌的血流量,调整止血带的松紧程度,使血流量控制在上止血带前的30%。30只大鼠随机分成3组,分别为缺血再灌注组(n=10)、缺血预处理组(n=10)、缺血预处理+NAME组(n=10)。应用尼克酰胺腺嘌呤二核苷酸黄递酶2+2+(NADH)染色,检测股四头肌各型肌纤维横截面积,钙-腺苷三磷酸酶(Ca-ATPase)染色,观察细胞膜CaATPase分布。透射电镜观测肌细胞的超微结构变化。结果缺血再灌注组出现明显肌纤维破裂溶解,许多白细胞浸润,电镜下线粒体中含有大量空泡变性、肌纤维断裂、溶解和"Z线"排列整齐膜脂质过氧化物的增加。与缺血再灌注组相比,缺血预处理组显示了轻微的损害,正常的纤维和血管变形少,股四头肌各型肌纤维横2+截面积降低,细胞膜Ca-ATPase数量增加。缺血预处理+NAME组与缺血再灌注组相比没有明显改变。结论缺血预处理对大鼠骨骼肌缺血再灌注损伤有明显保护作用,NO参与这一保护作用。     

Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning

Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 min occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 min occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for two or three cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with three cycles of 15 min performed immediately before stroke reduced infarct size from 47.7+/-7.6% of control ischemia to 9.8+/-8.6%; at two cycles of 15 min, infarct was reduced to 24.7+/-7.3%; at two cycles of 5 min, infarct was not reduced. Delayed preconditioning with three cycles of 15 min conducted 2 days before stroke also reduced infarct to 23.0+/-10.9%, but with two cycles of 15 min it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with three cycles of 15 min performed 12 h before stroke also reduced infarct to 24.7+/-4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia.     

缺血预处理对肝硬化大鼠肝脏缺血再灌注中肝细胞凋亡的影响

目的:探讨缺血预处理(IPC)在肝硬化大鼠肝缺血再灌注(I/R)损伤的拮抗作用及其机理。方法:Pringle法复制肝I/R模型,将肝硬化大鼠随机分为3组:A组:肝缺血前给予1个IPC处理(缺血5min,灌注5min);B组:肝缺血前给予1个IPC处理(缺血10min,灌注10min);C组:对照组,单纯肝门血流阻断。肝缺血时间为30min,再灌注6h。测定各组的血清谷丙转氨酶(ALT)、肝组织Fas-mRNA表达、caspase-3活性和肝细胞凋亡。结果:经IPC处理后,大鼠7d生存率为100%,而无IPC处理组即为62.5%。再灌注6h,A、B2组的ALT明显低于C组,P＜0.01,A组的ALT亦明显低于B组,P＜0.01。检测A、C2组的肝组织Fas-mRNA表达、caspase-3活性和肝细胞凋亡发现,A组的上述指标均比C组低,P＜0.01。结论:IPC对肝硬化大鼠肝I/R损伤有显著的对抗作用,其中以缺血5min和灌注5min的IPC的作用较强。IPC的保护机理是通过下调Fas-mRNA的表达、抑制caspase-3活性,从而减少肝细胞凋亡来实现的。     

肢体缺血预处理大鼠肝损伤保护效应中内皮素1的变化和意义

背景：研究体内最强的缩血管物质内皮素1在肢体缺血预处理保护大鼠肢体缺血再灌注后肝损伤中的变化和意义,有助于从肝脏微循环角度探讨肢体缺血预处理的保护作用。 目的：探讨内皮素1在肢体缺血预处理保护大鼠肢体缺血再灌注后肝损伤中的变化和意义。 方法：雄性Wistar大鼠随机分为对照组、肢体缺血再灌注组和肢体缺血预处理组。肢体缺血预处理组以橡皮带预先阻断双后肢血流5 min,然后恢复血流灌注5 min,反复4次进行缺血预处理。然后肢体缺血再灌注组和肢体缺血预处理组以橡皮带环绕结扎大鼠双后肢根部,阻断血流4 h后松解,恢复血流灌注4 h制备肢体缺血再灌注模型,并于再灌注前20 min于左侧颈外静脉插管滴注生理盐水。对照组双后肢松弛环绕橡皮带但不阻断血流,其后操作同肢体缺血再灌注组。 结果与结论：大鼠肢体缺血再灌注后血浆内皮素1、透明质酸酶、丙二醛、谷丙转氨酶、谷草转氨酶水平和肝组织内皮素1、丙二醛、髓过氧化物酶水平均明显升高(P < 0.05),肢体缺血预处理干预后上述指标均明显降低(P < 0.05)。光镜下可见肢体缺血再灌注组肝细胞肿胀,肝索排列不规则;肢体缺血预处理组上述损伤表现减轻。结果可见大鼠肢体缺血预处理对肢体缺血再灌注后肝损伤的保护作用可能与抑制了内皮素1的缩血管作用从而改善肝脏的微循环有关,也可能与内皮素1含量的降低减少了白细胞过度聚集活化和减弱脂质过氧化有关。     

CGRP通过抑制TNF-α介导单磷酰脂A对大鼠小肠的预适应延迟保护作用

目的: 探讨降钙素基因相关肽(CGRP)介导的单磷酰脂A(MLA)对大鼠小肠的预适应延迟保护作用是否通过抑制肿瘤坏死因子α(TNF-α)而产生。方法: 通过给予MLA(500 μg·kg^-1,ip)药物预适应,利用在体缺血再灌注(I/R)和原位灌流模型,检测外周血、灌流液和组织中乳酸脱氢酶(LDH)活性、丙二醛(MDA)含量和组织形态学改变以显示缺血再灌注损伤和药物的作用;通过放射免疫法测定血浆中CGRP和TNF-α含量探讨MLA预适应对大鼠小肠保护作用的机制。结果: 与I/R组相比,给予MLA后可使I/R组LDH活性和MDA含量明显降低(P<0.05);同时MLA使I/R损伤大鼠CGRP含量显著升高,TNF-α含量下降(P<0.01)。使用CGRP拮抗剂CGRP_8-37及辣椒素(capsaicin)耗竭CGRP后,均可消除MLA的这一作用。结论: MLA对在体、原位灌流大鼠小肠均诱导产生预适应的延迟保护作用;CGRP可能通过抑制TNF-α的产生而介导MLA诱导的预适应延迟保护作用。     

Contribution of Glucocorticoid Hormones to the Gastroprotective Effect of Ischemic Preconditioning in Rats in Normal Conditions and In Prostaglandin Deficiency

The aim of the present work was to study the contribution of glucocorticoid hormones to the gastroprotective effects of ischemic preconditioning in a gastric ischemia/reperfusion model in rats with normal and deficient prostaglandin production. The contribution of glucocorticoids was evaluated by adrenalectomy followed by corticosterone replacement therapy and transient inhibition of corticosterone synthesis with metyrapone. Prostaglandin synthesis was blocked with indomethacin. Gastric ischemia was created by compression of the celiac artery in anesthetized rats. Ischemic preconditioning (0.5 h ischemia/reperfusion) stimulated corticosterone production and decreased the formation of gastric erosions due to 3.5 h ischemia/reperfusion. Adrenalectomy and administration of metyrapone prevented the gastroprotective effect of ischemic preconditioning on the backgrounds of both normal and deficient prostaglandin production. Corticosterone replacement therapy restored the effect of ischemic preconditioning in adrenalectomized rats, even in conditions of blockade of prostaglandin synthesis. Thus, glucocorticoid hormones make a contribution to the gastroprotective effect of ischemic preconditioning in conditions of normal prostaglandin production, as well as in conditions of blockade of prostaglandin synthesis.     

Ischemic preconditioning prevents protein aggregation after transient cerebral ischemia

Transient cerebral ischemia leads to protein aggregation mainly in neurons destined to undergo delayed neuronal death after ischemia. This study utilized a rat transient cerebral ischemia model to investigate whether ischemic preconditioning is able to alleviate neuronal protein aggregation, thereby protecting neurons from ischemic neuronal damage. Ischemic preconditioning was introduced by a sublethal 3 min period of ischemia followed by 48 h of recovery. Brains from rats with either ischemic preconditioning or sham-surgery were then subjected to a subsequent 7 min period of ischemia followed by 30 min, 4, 24, 48 and 72 h of reperfusion. Protein aggregation and neuronal death were studied by electron and confocal microscopy, as well as by biochemical analyses. Seven minutes of cerebral ischemia alone induced severe protein aggregation after 4 h of reperfusion mainly in CA1 neurons destined to undergo delayed neuronal death (which took place after 72 h of reperfusion). Ischemic preconditioning reduced significantly protein aggregation and virtually eliminated neuronal death in CA1 neurons. Biochemical analyses revealed that ischemic preconditioning decreased accumulation of ubiquitin-conjugated proteins (ubi-proteins) and reduced free ubiquitin depletion after brain ischemia. Furthermore, ischemic preconditioning also reduced redistribution of heat shock cognate protein 70 and Hdj1 from cytosolic fraction to protein aggregate-containing fraction after brain ischemia. These results suggest that ischemic preconditioning decreases protein aggregation after brain ischemia.     

缺血后处理对抗大鼠离体心脏缺血再灌注损伤及其作用机制

目的： 研究缺血后处理（postconditioning）对抗大鼠离体心脏缺血再灌注损伤及其作用机制。方法：采用SD大鼠心肌缺血/再灌注模型，并于再灌注一开始即给予3次全心停灌30 s，再灌30 s处理作为缺血后预处理。记录心肌收缩功能指标，以Even’s blue-TTC法监测心肌梗死范围，并对心律失常严重程度进行定量分析。结果：缺血后处理组左室峰压（LVSP）、最大左室收缩速率（+dp/dt_max）以及心率明显高于缺血对照组。缺血后处理可明显缩小心肌梗死范围（22.97%±3.96% vs 缺血对照组 44.30%±13.61%，P<0.01）。观察复灌10 min时心律失常评分发现，缺血后处理组明显低于缺血对照组。缺血后处理组和缺血预处理组具有类似的心肌保护作用。5-HD组LVSP和+dp/dt_max低于缺血后处理组，心律失常评分增高，心肌梗死范围扩大。结论: 缺血后处理对大鼠缺血再灌注损伤具有心脏保护作用，其作用机制可能是部分通过激活线粒体ATP依赖性钾离子(mitoK_ATP)通道起作用。     

Troxerutin Preconditioning and Ischemic Postconditioning Modulate Inflammatory Response after Myocardial Ischemia/Reperfusion Injury in Rat Model

Protective effects of ischemic postconditioning in myocardial ischemia/reperfusion (I/R) injury have been ever demonstrated, but the exact mechanisms remain unclear. Because of their multiplex activities, using natural pharmaceuticals seems to be clinically interesting. The aim of present study was to investigate the effects of troxerutin preconditioning and ischemic postconditioning on inflammatory responses after myocardial I/R injury in a rat model. Twenty-four Wistar rats were divided into four groups as the control, troxerutin receiving (TXR), postconditioning receiving (PostC), and combined therapy (TXR + PostC). Rats’ isolated hearts underwent 30-min LAD regional ischemia followed by 45-min reperfusion. Troxerutin was orally administered for a month before I/R. Ischemic PostC was applied by alternative three cycles of 30-s R/I at the onset of reperfusion. The coronary effluent and ischemic left ventricular samples were used to determine the activities of creatine kinase (CK), intercellular adhesion molecule-1 (ICAM-1), interlukin-1beta (IL-1β), tumor-necrosis factor (TNF-α), and also histopathological studies. Pretreatment of rats with troxerutin significantly reduced myocardial inflammatory cytokines TNF-α and IL-1β levels and ICAM-1 activity after I/R insult compared to those of control I/R hearts (P?<?0.05). Application of PostC showed similar impacts on those parameters. In fact, anti-inflammatory mechanisms of both treatments were associated with their protective effects against myocardial damages causing from I/R injury. Pretreatment with troxerutin as well as postconditioning can induce cardioprotection through prevention of the cell-cell interaction and release of inflammatory mediators, minimizing I/R pathological changes in myocardial cells. These two treatments may share same mechanisms in their actions since they showed no significant additive effects.     

非创伤性预处理在离体心脏抗再灌注损伤中作用机制的探讨

目的:观察非创伤性肢体缺血预处理对大鼠离体再灌注心肌是否有保护作用。方法:实验采用体重(250±30)gSD雄性大鼠25只随机分成3组,在Langendorff装置上对大鼠离体心脏进行灌流。对照组(C,n=8):在灌注全程均用富氧K-H液(充以95%O₂+5%CO₂),在恒压(8.33kPa)、恒温(37℃)条件下灌注;缺氧/复氧组(A,n=8):预灌15min后,灌注心脏先全心缺血缺氧15min,随后15min复氧再灌注(37℃);非创伤性肢体缺血预处理组(N-WIP,n=9):先将大鼠双后肢捆绑5min,松开5min,反复4次后,随后的方法同R组。在相应时点分别测定冠脉流出液和心肌匀浆中超氧化物歧化酶(SOD)活性,Ca²⁺-Mg²⁺-ATP酶活性和丙二醛(MDA)含量,同时记录心肌细胞的单相动作电位(MAP)和心肌收缩张力曲线。结果:非创伤性肢体缺血预处理能使再灌注心律失常发生率显著低于A组;心肌组织中MDA含量显著低于A组,心肌组织中SOD活性显著高于A组,心肌细胞的膜电位、Ca²⁺-Mg²⁺-ATP酶活性及肌张力较稳定。结论:非创伤性肢体缺血预处理对大鼠离体再灌注心肌有明显的保护作用,可能是通过增强心肌的抗氧化能力、稳定心肌Ca²⁺-Mg²⁺-ATP酶活性和膜相结构等途径,提高心肌细胞对再灌注损伤的抵抗力。     

缺血预处理快速效应对兔急性缺血脊髓的保护作用

目的:探讨缺血预处理快速相对兔腹主动脉短暂阻断致缺血脊髓的保护作用。方法:36只雄性新西兰兔随机分成3组(n=12):即缺血再灌注损伤组(IR组)、缺血预处理组(IPC+IR组)及假手术组(Sham组)。IR组阻闭兔腹主动脉肾下段20min,复制兔脊髓缺血损伤模型;IPC+IR组预先阻闭腹主动脉肾下段6min,再灌注30min后再次阻闭腹主动脉肾下段20min;Sham组除不夹闭腹主动脉外,其余处理同IR组。再灌注后8h、12h、24h和48h分别对动物神经功能评分,然后,处死动物取脊髓(L_5-7),分别行组织病理学观察及测定脊髓组织中Na⁺,K⁺-ATP酶的活性。结果:Sham组及IPC+IR组神经功能评分各时点均明显高于IR组(P＜0.01);Sham组及IPC+IR组脊髓前角正常神经细胞数明显多于IR组(P＜0.01);Sham组及IPC+IR组脊髓组织中Na⁺,K⁺-ATP酶的活性明显高于IR组(P＜0.01)。结论:缺血预处理快速相对兔急性缺血脊髓有显著的保护作用,这种保护作用可能与稳定Na⁺,K⁺-ATP酶的活性有关。     

Pretreatment with tyrosine kinase inhibitor attenuates the reduction of apoptosis 24 h after ischemic preconditioning

We investigated whether ischemic preconditioning (PC) attenuates ischemia/reperfusion-induced injury in part by decreasing apoptosis and whether tyrosine kinase (TK) can regulate the signaling pathway leading to apoptosis in delayed cardioprotection. Six groups of rabbits were studied in the early phase (EP) and in the delayed phase (DP): (1) sham-operated control animals were received vehicle only (Veh-sham); (2) rabbits that received I.V. genistein (a nonspecific TK inhibitor) 10 min before ischemia (Gen-sham); (3) rabbits that received I.V. daidzein (an inactive structural analog of genistein) 10 min before ischemia (Dzn-sham); (4) rabbits preconditioned with 4 cycles of 5-min occlusion of left anterior descending coronary artery (LAD) and 10-min reperfusion (PC); (5) rabbits that received I.V. genistein, 10 min before PC (Gen-PC); (6) rabbits that received I.V. daidzein 10 min before PC (Dzn-PC). All rabbits underwent 30-min ischemia followed by 180-min reperfusion. Infarct size in the PC, Gen-PC, and Dzn-PC groups in the EP was significantly (p < 0.0001) reduced relative to controls Gen and Dzn. Delayed cardioprotection was blocked significantly (p < 0.0001) by genistein. In the EP, apoptosis was significantly (p < 0.0001) decreased in PC, Gen-PC, and Dzn-PC groups relative to controls Gen and Dzn. In the DP, a reduction of apoptosis was not seen in the Gen-PC group. This study suggests that PC reduces ischemic injury in part by decreasing apoptosis after ischemia/reperfusion and also that TK phosphorylation is involved in the signal transduction cascade leading to the decline of apoptosis in the DP.