银杏黄酮磷脂复合物对大鼠心肌再灌注血管内皮损伤的保护作用

目的:探讨银杏黄酮磷脂复合物对大鼠心肌缺血再灌注血管内皮损伤的保护作用。方法:健康Wister大鼠40只,随机分为假手术组、模型组、银杏黄酮组及银杏黄酮磷脂复合物组,每组10只,检测各组血浆内皮素(ET1)、前列环素(PGI2)、血栓素A2(TXA2)水平及血清一氧化氮(NO)、丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性。结果:银杏黄酮磷脂复合物对心肌缺血30min再灌注120min大鼠,可明显降低血清NO及MDA含量,而使SOD活性增强,亦使血浆ET1、TXA2水平下降,PGI2水平及PGI2/TXA2比值明显增高,且变化较银杏黄酮显著。结论:银杏黄酮磷脂复合物对大鼠心肌再灌注血管内皮损伤具有明显的保护作用,可能与其增强抗氧化酶活性,减少自由基对内皮细胞的氧化损伤,减少内源性血管活性物质ET1释放,纠正PGI2/TXA2失衡等机制有关。     

抗氧化活性物质对心肌缺血再灌注损伤的保护机制研究进展

摘要：抗氧化活性物质种类众多,来源广泛且具有安全无毒、抗氧化应激、抗炎及抗凋亡等特性。对于心肌缺血缺氧,再灌注是现今治疗的有效途径,但缺血再灌注造成的氧自由基的大量产生、白细胞的炎症作用以及进而引起的细胞凋亡等损伤暂且无法避免。目前研究显示,抗氧化物质对缺氧再灌注保护作用明显。本文就现研究的抗氧化肽类、苷类和黄酮类3类抗氧化活性物质对心肌缺血再灌注损伤的保护剂量、保护能力、所涉及的信号通路与分子机制进行论述总结,旨为心肌缺血再灌注损伤的相关研究和临床应用提供理论依据。     

槲皮素的药理作用研究近况

槲皮素具有广泛的药理作用。有抗氧化及清除氧自由基作用、能降低血压 ,保护心肌缺血再灌注损伤 ,有免疫增强功能及抗癌、抗菌、抗病毒和镇痛等作用。     

卡托普利对大鼠心肌缺血再灌注损伤的保护作用

采用大鼠离体工作心脏,观察卡托普利(CAP)对心肌缺血再灌注损伤的保护作用。结果表明:CAP 减少心肌肌酸磷酸激酶(CPK)释放、减少心肌丙二醛(MDA)生成、降低心肌细胞内钙含量、减少再灌注诱发的室颤(VF)和室速(VT)的发生率,并对心肌超微结构具有保护作用。作者还把CAP 和超氧化物歧化酶(SOD)作了比较。提示CAP 具有自由基清除作用,对心肌缺血再灌注损伤具有保护作用。     

丙泊酚通过激活PI3K-Akt信号转导通路抑制缺氧/复氧损伤致乳鼠心肌细胞凋亡

<正>丙泊酚是临床常用静脉麻醉药,有清除自由基抗氧化作用。既往研究表明,丙泊酚对心肌缺血再灌注损伤有保护作用[1]。心肌细胞凋亡是心肌缺血再灌注损伤心肌细胞死亡的主要方式之一,已证实丙泊酚能够抑制心肌细胞凋亡而发挥心肌保护作用[2],但其机制尚有待进一步明确。本研究通过建立离体乳鼠心肌细胞缺氧/复氧损伤模型,观察丙泊酚对心肌细胞凋亡的影响以及磷酸化-Akt(p-Akt)蛋白表达变化,进一     

3，6—（二甲氨基）—二苯并碘杂六环柠檬酸盐保护大鼠缺血再灌注心肌与抗脂质过氧化的关系

在大鼠在体心肌缺血再灌注模型上，观察了３、６（二甲氨基）二笨并碘杂六环柠檬酸盐（１６５）的抗心肌缺血再灌注损伤及抗脂质过氧化作用结果表明１－６５能明显改善缺血再灌注所致的心肌光镜及电镜下细胞结构损伤，升高心肌超氧化物歧化酶和谷胱甘肽过氧化物酶活性，减少丙二醛生成提示Ｉ６５对心肌缺血再灌注损伤的保护作用与保护氧自由基清除酶的活性．防止膜脂质过氧化有关     

灯盏花中焦袂康酸苷抗大鼠脑缺血再灌注损伤的研究

目的：研究灯盏花中焦袂康酸苷(ES)对大鼠脑缺血再灌注损伤的保护作用,及体外抗氧化和抗活性氧作用。方法：采用尼龙线栓塞大鼠大脑中动脉制备大鼠局灶性脑缺血再灌注模型,比色法测定药物体外抗氧化和抗活性氧作用。结果：在大鼠脑缺血再灌注损伤模型上,ES2～10mg／kg可显著降低大鼠行为评分,减轻缺血侧脑半球水肿程度,缩小脑梗死面积,且具有显著的体外抗氧化和抗活性氧作用。结论：灯盏花中ES对大鼠脑缺血再灌注损伤有保护作用,其抗氧化和抗活性氧作用可能是其保护作用机制之一。     

白藜芦醇预处理对心肌缺血/再灌注损伤的保护作用

目的:观察白藜芦醇预处理对心肌缺血再灌注损伤的保护作用.方法:45只雄性SD大鼠随机分为假手术组、缺血再灌组及白藜芦醇预处理组,结扎左冠状动脉制作心肌缺血再灌注模型,比较各组左室最大收缩压(LVSP)、左室等容收缩/舒张期压力上升最大速率(LVdP/dtmax),心肌一氧化氮(NO)、丙二醛(MDA)含量变化及心肌梗死范围.结果:白藜芦醇预处理组LVSP、LVdP/dtmax较缺血再灌组显著升高,心肌NO含量显著升高、MDA含量则显著降低,心肌梗死范围明显减小.结论:白藜芦醇预处理对心肌缺血再灌注损伤有明显保护作用,其机制与白藜芦醇抗氧化、清除自由基及增加NO合成有关.     

银杏黄酮磷脂复合物对血管内皮保护作用初探

目的:探讨银杏黄酮磷脂复合物对大鼠缺血再灌注状态下血管内皮的保护作用。方法:健康Wister大鼠40只,随机分为假手术组、模型组、银杏黄酮组及银杏黄酮磷脂复合物组,每组10只,检测各组血浆内皮素(ET1)、血清一氧化氮(NO)水平,并取心尖部心肌做电镜,观察血管内皮的显微结构变化。结果:大鼠在心肌缺血30min再灌注120min状态下,银杏黄酮磷脂复合物可明显降低血清NO含量,亦使血浆ET1水平下降,同时改善血管内皮超微结构的破坏程度,且变化较银杏黄酮组显著。结论:银杏黄酮磷脂复合物对大鼠心肌再灌注血管内皮损伤具有保护作用,可能与其减少自由基对内皮细胞的氧化损伤,减少内源性血管活性物质ET1释放有关。     

3,6—（二甲氨基）—二苯并碘杂六环柠檬酸盐保护大鼠缺血…

在大鼠在体心肌缺血再灌注模型上，观察了３，６－（二甲氨基）－二苯并碘杂六环柠檬酸盐（Ｉ－６５）的抗心肌缺血再灌注损伤及抗脂质过氧化作用。结果表明Ｉ－６５能明显改善缺血再灌注所致的心肌光镜及电镜下细胞结构损伤，升高心肌超氧化物歧人酶和谷胱甘肽过氧化物酶活性，减少丙二醛生成，提示Ｉ－６５对心肌缺血再灌注损伤的保护作用与保护氧自由基清除酶的活性，防止膜脂质过氧化有关。     

Comparative effects of flavonoids on oxidant scavenging and ischemia-reperfusion injury in cardiomyocytes

Since flavonoids scavenge reactive oxygen species, they may potentially protect against ischemia/reperfusion injury. This study compared the scavenging capacity of specific flavonoids towards different reactive oxygen species. Whether the differential oxidant scavenging capacity correlated with their protective efficacy in ischemia/reperfusion injury of cardiomyocytes was determined. The free radical scavenging capacity of five flavonoids (wogonin, baicalin, baicalein, catechin and procyanidin B2) was analyzed using electron spin resonance spectrometry for 3 radicals: 1,1-diphenyl-2picrylhydrazyl (DPPH), superoxide and hydroxyl radical. A well-established chick cardiomyocyte model of ischemia (1 h)/reperfusion (3 h) was used to evaluate flavonoid-induced protection against ischemia/reperfusion injury in chronic treatment (pretreated 72 h and treated through ischemia/reperfusion) and acute treatment protocols (during ischemia/reperfusion or only at reperfusion). The cell viability was assessed by propidium iodide. The DPPH scavenging was most significant with catechin, followed by procyanidin B2, baicalein, baicalin, and wogonin. The superoxide scavenging was, similarly, most significant with catechin, followed by baicalein, procyanidin B2, and baicalin. For hydroxyl radical, only baicalein showed a significant scavenging capacity (>50% reduction in ESR signal). For the cardiomyocyte studies, all flavonoids but wogonin showed protection against ischemia/reperfusion injury in the chronic treatment protocol. When flavonoids were administered only during ischemia/reperfusion, baicalein, procyanidin B2, and catechin significantly reduced cell death. If flavonoids were administered just at reperfusion, only baicalein and procyanidin B2 had protective effects, and the efficacy was less. Flavonoids possess specific but differential radical scavenging capacity, which, in conjunction with the timing of treatment, affects their protective efficacy in cardiomyocytes exposed to ischemia/reperfusion.     

前列地尔与川芎嗪、黄芪合用对大鼠心肌缺血再灌注损伤的保护作用

目的 :观察前列地尔与川芎嗪 (LT )、黄芪(AM ) 3药合用对大鼠心肌缺血再灌注损伤的保护作用。方法 :采用在体大鼠开胸结扎冠状动脉左室支 30min后 ,松扎再灌注 60min造成心肌缺血再灌注模型并以 0 .9%氯化钠注射液为模型对照 ,观察 3药 :前列地尔 31.2 5μg·kg- 1,川芎嗪 2 5mg·kg- 1,黄芪 4 15mg·kg- 1合用对再灌注心肌组织中超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶(GSH PX)活力 ,丙二醛 (MAD)、Ca2 +含量及血清肌酸磷酸激酶同功酶 (CK MB)含量的变化 ,并同时心电图监测心律失常情况。结果 :与模型对照组相比3药合用可提高再灌注心肌组织中SOD ,GSH PX活力 ,差异有非常显著意义 (P <0 .0 1) ;并能降低再灌注心肌组织中MDA ,Ca2 +含量及血清CK MB含量 ,差异有非常显著意义 (P <0 .0 1) ;防止再灌注室性心律失常的发生 ,缩短心律失常的维持时间 ,降低ST段抬高的程度 ,差异有非常显著意义 (P <0 .0 1)。结论 :前列地尔与LT ,AM合用在保护心肌缺血再灌注损伤中有显著的作用 ,其保护作用主要与清除自由基有关     

淫羊藿总苷对缺血-再灌注损伤大鼠心肌的保护作用

目的探讨淫羊藿总苷对缺血 再灌注损伤大鼠心肌的保护作用及其机制。方法通过结扎大鼠左冠状动脉前降支(LAD)后再灌注     

Functional and analytical evidence for scavenging of oxygen radicals by L-arginine

L-Arginine, the substrate of nitric oxide synthase, is known to exert favorable effects in the prevention and treatment of cardiovascular diseases. In several conditions, including atherosclerosis and ischemia/reperfusion, where oxygen metabolites are thought to mediate endothelial and myocardial injury, L-arginine has protective effects. Here we studied the mechanisms by which L-arginine protects against oxygen radical-induced myocardial injury. Buffer-perfused rat hearts were subjected to oxygen radicals generated by electrolysis or to hypoxanthine and xanthine oxidase, which generates superoxide anions (O(2)). Both sources of radicals impaired myocardial contractility, whereas L-arginine prevented the impairment. The observation that D-arginine as well as nitric oxide synthase inhibitors, such as N(G)-nitro-L-arginine but not glycine, had similar cardioprotective effects indicated that the protection might be due to a direct chemical interaction of L-arginine and its derivatives with oxygen radicals. In support, L-arginine and the derivatives prevented the formation of O(2) as determined by sensitive standard methods, whereas glycine did not. The radical scavenging activity of L-arginine and derivatives was dose-dependent, with an apparent rate constant of approximately 4.8 x 10(3) M s(-1) for the reaction of L-arginine with O(2) as determined by electron paramagnetic resonance spectroscopy using 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine (TEMPONE-H) as spin trap. In summary, the results of this study demonstrate protective effects of L-arginine against oxygen radical-induced cardiac injury by free radical scavenging.     

莲房原花青素对大鼠心肌缺血再灌注损伤的保护作用

目的探讨莲房原花青素(LSPC)对大鼠心肌缺血再灌注损伤的作用。方法用麻醉大鼠冠脉结扎30 min后，再灌注45 min造成心肌损伤模型。离体大鼠心脏经停灌30 min后，用正常K-H液复灌30 min，造成心肌损伤模型。均于实验前给予药物或生理盐水。结果LSPC可降低复灌后血清ET和Ang II的浓度，抑制MDA含量升高，并保持SOD活性及NO的水平。心脏复灌以后冠脉流量和心率明显恢复，心肌细胞酶CK和LDH漏出减少，心肌组织黄嘌呤氧化酶(XO)的活性降低，心肌超微结构的病理变化改善等。结论LSPC对整体及离体大鼠心肌缺血再灌注损伤具有保护作用。     

维生素E在大鼠肝脏缺血再灌注损伤中的作用

目的探讨维生素E在肝组织缺血再灌注(I/R)损伤的保护机制及对缺血预处理(IP)的影响。方法采用大鼠原位半肝缺血再灌注和缺血预处理模型,缺血前通过灌胃给予维生素E(250mg/kg),分析血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)、全血还原型谷胱甘肽(GSH)、肝组织脂质过氧化物(LPO)、超氧化物歧化酶(SOD)含量及肝组织病理改变等各项指标。结果I/R导致明显的肝损伤,IP减轻肝I/R损伤,维生素E能减轻肝组织缺血再灌注损伤,但可以部分抵消IP的保护作用。结论维生素E能减轻肝组织缺血再灌注损伤,其作用是通过减少氧自由基产生而实现的。IP对鼠肝I/R有明显的保护作用,IP期间产生的一定量的自由基,对随后的I/R的保护作用具有重要意义。维生素E导致氧自由基减少是肝IP保护作用的不利因素。     

Reactive oxygen species in myocardial reperfusion injury: from physiopathology to therapeutic approaches

Myocardial ischemia is a major cause of morbidity and mortality in the world. Although restoration of blood flow after prolonged ischemia is essential for cardiomyocytes salvation and to limit myocardial damage and cardiac dysfunction, reperfusion itself exacerbates myocardial injury. Considerable evidence attributes reactive oxygen species (ROS), produced either by the myocardium itself or by infiltrating inflammatory cells, as an early event in this process. Once produced, ROS can lead to cellular damage through a number of pathways including direct damage to membranes and proteins or indirect damage through the activation of pro-apoptotic pathways. While using antioxidants to scavenge free radicals or targeting the sources of ROS, such as xanthine oxidase, may be potential attractive approaches to reduce myocardial reperfusion injury, clinical trials using antioxidant therapies have been largely disappointing. Neither oxidant scavengers like N-acetylcysteine and vitamins E and C, nor xanthine oxidase inhibitor allopurinol have provided indisputable evidence of a clinical benefit despite numerous favourable studies in animal models. Evidence to support a role of ROS in myocardial injury reperfusion is strong, but the clinical approach used has so far been inadequate. Absence of optimal pharmacology, variation in end-points used and low specificity of the compounds used have often been pointed out. In addition, the efficacy of antioxidants is often evaluated based on indirect biomarkers, which are prone to variation. Thus, clinical trials could be improved by the standardisation of the methods to measure oxidative stress and their impact on prognosis outcome.     

Redox Signaling Pathways Involved in Neuronal Ischemic Preconditioning

There is extensive evidence that the restoration of blood flow following cerebral ischemia contributes greatly to the pathophysiology of ischemia mediated brain injury. The initiating stimulus of reperfusion injury is believed to be the excessive production of reactive oxygen (ROS) and nitrogen (RNS) species by the mitochondria. ROS and RNS generation leads to mitochondrial protein, lipid and DNA oxidation which impedes normal mitochondrial physiology and initiates cellular death pathways. However not all ROS and RNS production is detrimental. It has been demonstrated that low levels of ROS production are protective and may serve as a trigger for activation of ischemic preconditioning. Ischemic preconditioning is a neuroprotective mechanism which is activated upon a brief sublethal ischemic exposure and is sufficient to provide protection against a subsequent lethal ischemic insult. Numerous proteins and signaling pathways have been implicated in the ischemic preconditioning neuroprotective response. In this review we examine the origin and mechanisms of ROS and RNS production following ischemic/reperfusion and the role of free radicals in modulating proteins associated with ischemic preconditioning neuroprotection.     

RETRACTED: Effect of trimetazidine on renal ischemia/reperfusion injury in rats

There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of trimetazidine, in I/R induced renal failure in rats. The protective effect of trimetazidine (Tmz) against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague-Dawley rats using histopathological and biochemical parameters. In one set of experiments animals were unilaterally nephrectomized, and subjected to 45 min of left renal pedicle occlusion and in another set both the renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Trimetazidine (3 mg kg(-1), i.p.) was administered 30 min prior to ischemia and repeated 12 h after the first dose. At the end of the reperfusion period, rats were sacrificed. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, glutathione reductase (GR) catalase (CAT), and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with trimetazidine markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes. The findings imply that ROS play a causal role in I/R induced renal injury and trimetazidine exert renoprotective effects probably by the radical scavenging and antioxidant activities.     

Mechanisms of protective effects of berbamine on ischemia/reperfusion injury in isolated rat heart.

Isolated perfused rat heart model was used to observe the protective effects of berbamine on myocardial ischemia/reperfusion injury. The hearts were significantly injured by 40 min global ischemia followed by 20 min reperfusion. Berbamine could significantly improve heart function, prevent ventricular fibrillation, reduce CK release, preserve Na,K-ATPase activity, and reduce Na+ gain and K+ loss during ischemia and Ca2+ overload during reperfusion. With the use of low temperature ESR technique, in hearts subjected to 40 min ischemia and 15 sec reperfusion, oxygen-centered free radical signals became much more intense. In the presence of berbamine, these signals decreased. Results showed that berbamine could alleviate myocardial ischemia/reperfusion injury. This effect might be due to: 1) preserved myocardial Na,K-ATPase activity and inhibition of sodium overload at the end of ischemia, which might further lead to attenuation of reperfusion-induced calcium overload, and 2) reduction of oxygen free radical generation during reperfusion.