雌二醇对兔心肌缺血/再灌注损伤的急性保护作用

目的探讨17b-雌二醇（17b-E2）对兔在体缺血/再灌注（I/R）心肌的急性保护作用及其相关机制。方法通过结扎冠状动脉左前降支建立兔在体心肌I/R模型（心肌缺血40 min,再灌注3 h）;采用抽签法将24只健康雄性新西兰白兔随机分为两组（每组12只）,对照组：心肌缺血前静脉注入1 ml乙醇;实验组：心肌缺血前静脉注入10μg/kg 17b-E2。用酶联免疫吸附测定（ELISA）法分别于心肌缺血前、缺血40 min、再灌注1 h、2 h和3 h不同时间点检测血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）的含量;蛋白印迹法（Western blotting）测定心肌p38丝裂原活化蛋白激酶（MAPK）的表达;脱氧核苷酸转移酶介导的生物素脱氧尿嘧啶核苷酸缺口末端标记（TUNEL）法检测心肌细胞凋亡。结果缺血过程中,实验组TNF-α较对照组降低（F=0.007,P=0.001）,而IL-6变化不明显（F=0.616,P=0.095）;再灌注过程中,实验组TNF-α和IL-6的含量明显低于对照组（P〈0.01）;同时实验组p38MAPK的活性和心肌凋亡指数均明显低于对照组（45.07%±2.73%vs.61.25%±2.41%,t=-15.398,P=0.000;11.21%±3.85%vs.22.02%±4.49%,t=-6.332,P=0.000）。结论 17b-E2通过抑制炎症反应及抗凋亡途径减轻心肌I/R损伤,其作用可能是通过对p38MAPK的抑制而实现的。     

烟碱预处理对大鼠心肌缺血-再灌注损伤的保护作用

目的 探讨烟碱预处理对大鼠心肌缺血-再灌注损伤的保护作用及其可能机制.方法 30只健康雄性Sprague-Dawlay大鼠,体重200～250g,随机均分为缺血-再灌组(I-R组)、烟碱预处理组(N组)、假手术组(Sham组).测定三组血浆肌酸激酶同工酶(CK-MB)活性、丙二醛(MDA)含量和超氧化物岐化酶(SOD)活性,心肌组织中髓过氧化物酶(MPO)活性,电镜下观察缺血区心肌超微结构变化.结果 与Sham组比较,I-R组血浆CK-MB活性、MDA含量及心肌组织MPO活性均升高、血浆SOD活性降低(P<0.05或P<0.01);与I-R组比较,N组血浆CK-MB活性、MDA含量及心肌组织MPO活性均降低,血浆SOD活性升高(P<0.05或P<0.01),心肌病理学损伤减轻.结论 烟碱预处理可减轻大鼠心肌缺血-再灌注损伤,其机制可能与减少氧自由基生成、增强心肌抗氧化能力有关.     

心肌缺血再灌注损伤中线粒体的作用

心肌缺血再灌注损伤的本质是细胞凋亡，线粒体在调控细胞凋亡中起重要作用。心肌缺血再灌注过程中发生物质代谢改变，线粒体Ca^2 超载，氧自由基产生过多，这些引起心肌细胞凋亡的过程均涉及线粒体。线粒体最明显的变化是通透性增加，膜电位下降。     

凋亡在心肌缺血及再灌注损伤中的作用

凋亡是机体组织细胞的一种自主调节行为,其发生受基因调控。凋亡在心肌缺血及再灌注损伤中发挥着重要作用,本文就其对心肌缺血及再灌注损伤作用、可能机制和防治方法的研究进展作一综述。     

巯甲丙脯酸对心肌缺血再灌注损伤保护作用的研究进展

巯甲丙脯酸具有抗氧自由基作用,可提高心肌组织ATP及其合成底物水平,抑制参与心肌缺血再灌注损伤的内源性血管活性物质的合成及释放,促进具有抗心肌缺血再灌注损伤作用的内源性血管活性肽的合成及释放。本文综述巯甲丙脯酸心肌保护作用的研究进展。     

丙泊酚对心肌缺血-再灌注损伤的保护作用及其机制

心肌缺血后再灌注具有两重性，多数情况下，缺血后再灌注使心肌功能得到恢复，损伤的结构得到修复。但是有时缺血后再灌注不仅不能使心肌功能恢复，反而加重心脏的功能障碍和结构损伤，这种现象称为缺血一再灌注损伤(ischmia—reperfusion injury)。临床上，心肌再灌注损伤常出现在心肺复苏、体外循环、动脉搭桥术后，表现为心功能低下、严     

细胞凋亡与心肌缺血再灌注损伤

细胞凋亡是细胞主动死亡方式,其过程受自身基因如：ｍｙｃ,Ｐ５３,Ｆａｓ,ｂｃｌ－２等调控。业已证明,细胞凋亡是心肌缺血／再灌注损伤的特征之一,抑制细胞凋亡可预防缺血／再灌注损伤。本从细胞凋亡的特征、基因调控、检测方法以及心肌缺血／再灌注损伤过程中心肌凋亡证据等方面进行综述,并从细胞及分子水平探讨心肌缺血／再灌注缶伤的发病机制,为心肌保护提供理论依据。     

再灌注早期应用雌二醇对缺血鼠心肌的保护作用

目的　探讨再灌注早期应用 17β 雌二醇 (17β estradiol,E2 )对心肌缺血再灌注损伤 (MIRI)的影响。方法　采用Langendorff离体鼠心脏灌注模型 ,将 30只雌性卵巢切除 (OVX)大鼠随机均分为 3组。缺血再灌注组 (I R组 )用K H液预灌注 15min ,常温停灌 30min ,恢复K H液再灌注 30min。 0 1%二甲基亚砜组 (D组 )和 5 μmol LE2 组 (E组 )从再灌注第 6min起改用含相应药液的K H液灌注 2 5min ,余同I R组。记录各组心功能及冠脉流量 (CF) ,测量冠脉流出液中乳酸脱氢酶 (LDH)、肌酸磷酸激酶 (CPK)、心肌丙二醛 (MDA)含量及心肌超氧化物歧化酶 (SOD)活性的变化。结果　再灌 30min时 ,E组CF比I R、D组明显增加 (P <0 0 1) ;I R、D、E组心功能均降低 ,但I R和D组较E组更为显著 (P <0 0 1) ;E组SOD活性明显高于I R和D组 (P <0 0 1)而MDA、CPK和LDH的含量明显低于I R和D组 (P <0 0 1) ;I R组和D组之间未显示出统计学差异。结论　E2 可通过其抗氧化作用 ,防止MIRI。     

巯甲丙脯酸对心肌缺血再灌注损伤保护作用的研究进展

巯甲丙脯酸具有抗氧自由基作用，可提高心肌组织ＡＴＰ及其合成底物水平，抑制参与心肌缺血再灌注损伤的内源性血管活性物质的合成及释放，促进具有抗心肌缺血再灌注损作作用内源性血管活性肽的合成及释放。本文综合综巯甲丙脯酸心肌保护作用的研究进展。     

17-β-雌二醇对大鼠肝脏缺血再灌注损伤的保护作用及其机制

目的 探讨17-β-雌二醇对雄性大鼠肝脏缺血再灌注(I／R)损伤的保护作用及其机制。方法 采用大鼠部分肝脏缺血再灌注损伤模型，将健康雄性SD大鼠96只随机分成两组：A组(缺血再灌注组)，B组(17-β-雌二醇处理组)。每组分别随机取6只于缺血前、肝脏再灌注后1h、2h、4h、1d、3d、5d、7d时检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)和肿瘤坏死因子(TNF-α)水平，并进行统计学处理。结果 除缺血前和再灌注7d外A组动物在相应时点ALT、AST、LDH、TNF-α水平均高于B组，且A组动物肝功能恢复正常时间(与缺血前相比)迟于B组。结论 17-β-雌二醇对肝脏缺血再灌注损伤有显著的保护作用，并可缩短病程，其作用机制可能与17-β-雌二醇降低肝脏I／R时血清TNF-α水平有关。     

Cardioprotective Effect of Succinate Against Ischemia/Reperfusion Injury

(Received for publication on Sept. 12, 1996; accepted on May 12, 1997)     

细胞色素C在缺血/再灌注损伤中的作用

细胞色素C为线粒体呼吸链复合体Ⅲ的成分,在复合体Ⅲ和Ⅳ之间传递电子。许多因素可刺激细胞色素C从线粒体释放,一旦其释放到胞浆中就可依赖于细胞内ATP水平诱导细胞凋亡或坏死。研究表明缺血／再灌注损伤与细胞色素C释放密切相关。现从细胞色素C的结构和特性、释放及其调控、缺血再灌注损伤对细胞色素C释放的影响以及其在缺血再灌注损伤中的作用等方面进行综述。     

Cold Ischemia Time Influences Spermatogenesis in a Testicular Ischemia/Reperfusion Injury Model

Objective

To evaluate the influence of cold ischemia time on spermatogenesis in a rabbit model of testicular ischemia-reperfusion (I/R) injury.

Material and Methods

The testicular I/R model was established in 24 male white rabbits. The left testes were preserved using HC-A solution at 0°C to 4°C. Cold ischemia time was 1, 2, 4, and 6 hours. The right testes without vascular occlusion were used as autologous controls. Twenty-four hours after reperfusion, the animals were sacrificed, and samples were obtained at bilateral orchiectomy. Another 8 normal testes were used as normal controls. Testicular tissue Johnsen score, malondialdehyde concentration, and apoptosis index were used to evaluate spermatogenesis.

Results

The Johnsen score decreased and the apoptosis index increased with the duration of cold ischemia time in the I/R groups. The malondialdehyde concentration in the I/R groups was significantly higher than the sham and normal groups, and was highest at 4 hours of cold ischemia time.

Conclusion

Testicular I/R injury is highly related to cold ischemia time. In rabbit models, testis transplantation is best performed within 4 hours of cold ischemia with traditional hypothermic protection.     

心肌缺血/再灌注损伤中IGF的抗凋亡机制

胰岛素样生长因子对心肌缺血-再灌注损伤具有保护作用,它是通过代谢机制和细胞信号转导机制发挥抗心肌细胞凋亡的作用,现就其生理特点,对心肌的保护及抗凋亡机制进行综述。     

Hepatocellular Protein Profiles After Hepatic Ischemia/Reperfusion Injury With or Without Octreotide Preconditioning in a Rabbit Model

Hepatic ischemic/reperfusion injury (HIRI) is a major complication of liver resection and transplantation. Octreotide, a somatostatin analogue, has been used to treat hepatic fibrosis and portal hypertension; however, its function against HIRI remains unclear. To elucidate the effect of octreotide in HIRI, we investigated the hepatocellular protein profiles in response to octreotide preconditioning in a rabbit model by using proteomic analysis. Twenty-four rabbits were divided into 3 groups: the sham operative group (control), the ischemia/reperfusion group (IR), and the ischemia/reperfusion + octreotide group (IR+Oct). They were subjected to 30 minutes of normothermic ischemia followed by 120 minutes of reperfusion by using Pringle's maneuver method. Proteomic studies were then performed to compare the protein profiles of their left liver lobe. A total of 16 differential proteins were successfully identified. These findings suggest that octreotide might exert an effect against HIRI through up-regulating the expression of the anti-injury substances, such as heat-shock proteins 70 and 27 (confirmed by using Western blot analysis); significantly raising the phosphatidylethanolamine-binding protein that alleviates IR-related apoptosis; and down-regulating mitochondrial metabolic enzymes such as NADH2 dehydrogenase and triosephosphate isomerase.     

Mechanisms of Myocardial Cell Injury during Ischemia and Reperfusion

Ischemia in myocardial tissue results in impaired high energy phosphate production and diminished perfusion of the interstitial space. Reduction in the supply of ATP to the sarcolemmal and sarcoplasmic reticulum Na+ and Ca2+ pumps results in a rise in intracellular (Ca2+), which can exceed normal systolic levels within 10 to 15 minutes. Elevated (Ca2+)i can cause activation of proteases and phospholipases, which can damage the sarcolemma and release toxic metabolites, such as lysophospholipids. Oxygen free radicals can be produced by breakdown of nucleosides and accumulate in the interstitial space. Accumulation of metabolites intracellularly can cause cell swelling, which in addition to rigor due to ATP depletion, can stress the weakened sarcolemma, producing cell rupture and death. With reperfusion, additional injury to the myocyte may occur. Resupply of oxygen can result in a burst of oxygen free radical production. Resynthesis of ATP may sensitize the myofilaments to Ca2+, resulting in a hypercontracture that can further promote cell rupture. Resupply of ATP and washout of H+ may cause activation of Na/Ca2+ exchange, thus intensifying Ca2+ overload. Washout of the hypertonic interstitial space fluid may aggravate cell swelling and produce sarcolemmal rupture. Prevention or alteration of ischemic and reperfusion injury in myocardial cells is important clinically. Strategies currently being explored include reducing the rise in (Ca2+)i, which occurs during ischemia and reperfusion; inhibiting the actions of phospholipase on the cell membrane; decreasing free radical effects; and reducing stress on the sarcolemmal by prevention of cell swelling and hypercontracture.     

N-acetylcysteine Improves Cardiac Contractility and Ameliorates Myocardial Injury in a Rat Model of Lung Ischemia and Reperfusion Injury

ObjectivesLung ischemia and reperfusion (I/R) injury is the major complication subsequent to cardiopulmonary bypass surgery and lung transplantation. Lung I/R injury frequently induces cardiac dysfunction leading to significant mortality. So far, the literature on therapeutic interventions in cardiac dysfunction and myocardial injury is still scarce. In this study, we examined the efficacy of N-acetylcysteine (NAC) administration against lung I/R injury–induced cardiac dysfunction.MethodsLung ischemia was established by occluding the left lung hilum for 60 minutes, followed by 2 hours of reperfusion. Studies were performed in 3 groups: sham-operated (same surgical procedure except vessel occlusion; N = 8), lung I/R injury (N = 12), and NAC-administered group (N = 12). The cardiac function was assessed using simultaneous left ventricular (LV) pressure and volume measured via a high-fidelity pressure-volume catheter. Myocardial injury was assessed based on serum creatine kinase muscle brain fraction (CK-MB) and troponin I (cTnI) level, and lung injury based on the degree of protein concentration in lung lavage. We also examined the degrees of myocardial lipid peroxidation and hydroxyl radical production with and without NAC.ResultsDuring lung ischemia, LV stiffness increased with relative intact contractility. After 2 hours of reperfusion, LV contractility decreased with dilated and stiffened ventricle, along with apparent myocardial and lung injury. NAC administration effectively attenuated heart and lung injury, and ameliorated impaired LV contractility and stiffening resulting from lung I/R injury.ConclusionsNAC administration reduced lung I/R-induced increases in myocardial hydroxyl radical production and lipid peroxidation, and ameliorated LV contractility and stiffening.