外源性H2S吸入对大鼠肢体缺血／再灌注后心肌损伤的保护作用研究

目的 研究外源性H2S吸入对大鼠双下肢缺血/再灌注后心肌损伤的保护作用.方法 雄性Wistar大鼠23只,随机分为三组:①正常对照组( C组,8只);②缺血/再灌注组(I/R组,8只):应用止血带结扎构建大鼠双下肢缺血/再灌注模型,缺血4 h再灌注4 h.③H2S吸入组(H2S组,7只):大鼠双下肢缺血4 h,再灌注时给予含80 ppm H2S的合成空气持续吸入4 h.观察各组大鼠心肌病理、血浆H2S、肌酸激酶同工酶(CK-MB)、肌钙蛋白-T(TnT)、髓过氧化物酶(MPO)、肿瘤坏死因子-α(TNF-α)水平的变化及心肌胱硫醚-γ-裂解酶(CSE)活性、MPO、TNF-α水平的变化.以免疫组化法观察心肌细胞TNF-α的表达.结果 与C组比较,I/R组血浆CK-MB、TnT、MPO、TNF-α及心肌MPO、TNF-α水平明显上升(P＜0.05),血浆H2S及心肌CSE活性明显下降(P＜0.05),H2S吸入后血浆H2S及心肌CSE活性明显升高;同时,血浆CK-MB、TnT、MPO、TNF-α及心肌MPO、TNF-α水平明显降低(P＜0.05).心肌病理提示I/R组心肌明显肿胀、血管充血,心肌细胞间可见明显分叶核粒细胞浸润,红细胞漏出增多,H2S吸入后心肌损伤明显减轻.心肌TNF-α免疫组化提示I/R组心肌胞浆棕色染色颗粒较C组明显增多,H2S吸入后心肌胞浆棕色染色颗粒明显减少.结论 外源性H2S吸入可以通过降低炎细胞浸润及炎性细胞因子激活而对骨骼肌缺血/再灌注的心肌损伤发挥保护作用.     

大鼠心肌缺血再灌注损伤实验模型研究

目的:改进心肌缺血再灌注模型制备方法,提高造模成功率,以便使其能反复地多次进行心肌缺血再灌注实验和确保心肌缺血预处理实验顺利进行。方法:采用成年SD大鼠制作心肌缺血再灌注损伤模型,剪断肋骨同时结扎肋间动脉,不使用扩胸器,直接用结扎线将肋骨残端用力拉向两侧,充分暴露心脏;结扎冠状动脉操作在胸腔内进行。结果:用改进的方法造模成功率100%;用传统的方法造模的成功率为80%。应用此法造模进行反复多次缺血再灌实验的成功率为90%;而用传统的方法造模进行反复多次缺血再灌实验的成功率仅为10%。结论:改进后的方法简单易行,操作方便,成功率高。此法造模是目前完成心肌缺血再灌注实验比较好的模型,又是保证大鼠心肌缺血预处理实验成功的方法。     

Potential role of renin-angiotensin system blockade for preventing myocardial ischemia/reperfusion injury and remodeling after myocardial infarction

Experimental and clinical studies have demonstrated that myocardial ischemia induces activation of various components of the renin-angiotensin system (RAS), including angiotensinogen, renin, angiotensin-converting enzyme (ACE), angiotensins, and angiotensin receptors, in the acute phase of myocardial infarction and the postinfarction remodeling process. Pharmacological inhibition of the RAS by administration of renin inhibitors, ACE inhibitors, and angiotensin receptor blockers has shown beneficial effects on the pathological processes of myocardial infarction in both experimental animal studies and clinical trials. However, the potential mechanisms responsible for the cardioprotection of RAS inhibition remain unclear. In this review, we discuss roles of RAS blocking in the prevention of myocardial ischemia/reperfusion injury and postinfarction remodeling.     

Free radicals and myocardial ischemia and reperfusion injury

There is a growing body of evidence for the role of free radicals in mediating myocardial tissue injury during myocardial ischemia and in particular during the phase of myocardial reoxygenation. Associated with myocardial ischemia and reperfusion is the generation of oxygen-derived free radicals from a variety of sources that include the mitochondrial electron transport chain; the biosynthesis of prostaglandins; the enzyme xanthine oxidase; and circulating elements in the blood, with the polymorphonuclear neutrophil assuming a primary focus of attention. Experimental studies have shown that free radical scavengers (e.g., N-[2-mercaptopropionyl]glycine) and enzymes that scavenge or degrade reactive species of oxygen (superoxide dismutase or catalase) can reduce the mass of myocardial tissue that undergoes irreversible injury. Additionally allopurinol, which inhibits the enzyme xanthine oxidase, reduces ultimate infarct size, putatively by reducing the xanthine oxidase generation of superoxide anion. Neutrophils that enter the ischemically injured myocardium under the influence of chemotactic attraction and activation of the complement system generate and release highly reactive and cytotoxic oxygen derivatives that are destructive to the vascular endothelium and to the cardiac myocytes. Studies have documented that neutrophil depletion or suppression of neutrophil function (ibuprofen, nafazatrom, BW 755C, or more recently with prostacyclin or iloprost) results in a significant salvage of myocardial tissue that is subjected to a period of regional ischemia followed by reperfusion. Our current understanding of the events associated with myocardial ischemia suggests that within the ischemic myocardial region or area at risk, there is a population of cells that are reversibly injured and that reperfusion within a specified period (less than 3 hours) of time is capable of restoring the majority of the jeopardized cells to a normal status, but that the act of reperfusion itself will lead to the sudden demise of a fraction of the cells because of the cytotoxic effects of reactive species of oxygen derived from one or more of the sources indicated above. The efforts to minimize the amount of tissue that undergoes cell death as a result of myocardial ischemia demand that early reperfusion be established. However, the reintroduction of molecular oxygen and the circulating elements of the blood will be associated with an "explosive" and self-limited destruction of some of the myocardial cells in the area at risk.(ABSTRACT TRUNCATED AT 400 WORDS)     

Inhibitors of bradykinin-inactivating enzymes decrease myocardial ischemia/reperfusion injury following 3 and 7 days of reperfusion

Inhibitors of bradykinin (BK)-inactivating enzymes protect from myocardial ischemia/reperfusion injury after short periods of reperfusion. However, protection after 2 to 3 h of reperfusion does not mean that myocardium remains viable for an extended time. Therefore, we examined the effects of inhibitors of angiotensin-converting enzyme (ramiprilat), EP24.11 (cFP-F-pAB), and EP24.15 (cFP-AAF-pAB) in a chronic model of myocardial ischemia/reperfusion injury. A left descending coronary artery was occluded for 30 min in anesthetized rabbits. Saline, ramiprilat, or endopeptidase inhibitors were given after 27 min of occlusion. The BK(2) receptor antagonist HOE140 was administered in certain experiments. After ischemia, the occlusion was released, and the animal allowed to recover for 3 or 7 days. Surgery was then repeated, and the heart removed for determination of infarct size. In separate experiments, the heart was removed after 2 h of reperfusion for determination of BK tissue levels. Ramiprilat and endopeptidase inhibitors reduced infarct size at 3 and 7 days. Combining inhibitors further reduced infarct size after 3 days. The protective effect of the endopeptidase inhibitors was blocked by HOE140. Infarct sizes at 7 days were larger than at 3 days. The additive effect of multiple inhibitors was absent at 7 days. Ramiprilat and cFP-F-pAB significantly increased tissue BK levels. We conclude that inhibition of BK-inactivating enzymes protects endogenous BK from degradation and provides long-lasting protection from myocardial ischemia/reperfusion injury. A single treatment at the time of reperfusion does not prevent extension of the infarction between 3 and 7 days.     

Blockade of electron transport before cardiac ischemia with the reversible inhibitor amobarbital protects rat heart mitochondria

Cardiac ischemia damages the mitochondrial electron transport chain. Irreversible blockade of electron transport at complex I by rotenone decreases ischemic damage to cardiac mitochondria by decreasing the loss of cytochrome c and preserving respiration through cytochrome oxidase. Therapeutic intervention to protect myocardium during ischemia and reperfusion requires the use of a reversible inhibitor that allows resumption of oxidative metabolism during reperfusion. Amobarbital is a reversible inhibitor at the rotenone site of complex I. We asked whether amobarbital administered immediately before ischemia protected respiratory function. Isolated rat hearts were perfused for 15 min followed by 25-min global ischemia at 37 degrees C. Amobarbital-treated hearts received drug for 1 min before ischemia. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated after ischemia, and oxidative phosphorylation was measured. Amobarbital protected oxidative phosphorylation, including through cytochrome oxidase, in both SSM and IFM in a dose-dependent manner, with an optimal dose of 2 to 2.5 mM. Amobarbital also preserved cytochrome c content in both SSM and IFM. Thus, reversible blockade of the electron transport chain during ischemia protects mitochondrial respiration.     

In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury.

The cardioprotective effects of an mAb to P-selectin designated mAb PB1.3 was examined in a feline model of myocardial ischemia (MI) and reperfusion. PB1.3 (1 mg/kg), administered after 80 min of ischemia (i.e., 10 min before reperfusion), significantly attenuated myocardial necrosis compared to a non-blocking mAb (NBP1.6) for P-selectin (15 +/- 3 vs 35 +/- 3% of area at risk, P < 0.01). Moreover, endothelial release of endothelium derived relaxing factor, as assessed by relaxation to acetylcholine, was also significantly preserved in ischemic-reperfused coronary arteries isolated from cats treated with mAb PB1.3 compared to mAb NBP1.6 (67 +/- 6 vs 11 +/- 3, P < 0.01). This endothelial preservation was directly related to reduced endothelial adherence of PMNs in ischemic-reperfused coronary arteries. Immunohistochemical localization of P-selectin was significantly upregulated in the cytoplasm of endothelial cells that lined coronary arteries and veins after 90 min of ischemia and 20 min of reperfusion. The principal site of intracytoplasmic expression was in venous vessels. mAb PB1.3 significantly decreased (P < 0.01) adherence of unstimulated PMNs to thrombin and histamine stimulated endothelial cells in a concentration-dependent manner in vitro. These results demonstrate that PMN adherence to endothelium by P-selectin is an important early consequence of reperfusion injury, and a specific monoclonal antibody to P-selectin exerts significant endothelial preservation and cardioprotection in myocardial ischemia and reperfusion.     

心肌缺血再灌注损伤与热休克蛋白

目的:热休克蛋白是细胞在应激条件下产生的一类高度保守的蛋白质,它可以从抵抗损伤和加速修复两个方面对细胞进行保护。研究表明热休克蛋白对心肌缺血再灌注损伤有内源性的抵抗作用。本文对热休克蛋白及其内源性抵抗心肌缺血再灌注损伤的作用机制进行综述。资料来源:①从图书馆手工查阅相关领域的学术期刊,重点是核心期刊,查阅有关心肌损伤与热休克蛋白之间关系的文献,关键词为“心肌损伤、热休克蛋白、缺血再灌注”。②在cnki数据库及PubMed检索2000/2006心肌缺血再灌注损伤保护方面的文献资料,关键词是“心肌损伤、热休克蛋白”。资料选择:手工和应用计算机分别检索到13篇和29篇与热休克蛋白与心肌缺血再灌注损伤有关的文献。纳入标准:选择实验性文献,即一次性文献。对于内容相近的文献选择在核心期刊发表或年限较近的文章。排除标准:重复性研究。资料提炼:共得到35篇文献,其中2004/2006的文献有14篇,2000/2003的文献7篇。资料综合:热休克蛋白是细胞在应激情况下启动热休克基因从而产生的一种结构高度保守的蛋白质,几乎存在于从原核生物到真核生物的所有生物体。它具有非特异性、高度保守性、热休克蛋白70表达突出性、时间性、弱的ATP酶的活性和交叉耐受性等特性。热休克蛋白对细胞具有保护作用,主要表现在抵抗损伤和加速修复这两方面。20世纪80年代末,人们开始注意到热休克蛋白具有心肌保护作用,1988年,Currie等将SD大鼠进行热休克预处理,待其恢复24h后,进行离体心肌缺血再灌注,结果发现热休克组大鼠心肌缺血再灌注损伤后力学指标的恢复明显改善,心肌超微结构的损伤也有不同程度的减轻。热休克蛋白抵抗心肌缺血再灌注损伤的机制包括:稳定细胞内变性的蛋白质;减轻细胞内的离子紊乱;保护血管内皮细胞的功能;干扰应激所启动的细胞调亡程序等4个方面。结论:热休克蛋白对心肌缺血再灌注损伤具有内源性的抵抗作用。     

RhoA protects the mouse heart against ischemia/reperfusion injury

The small GTPase RhoA serves as a nodal point for signaling through hormones and mechanical stretch. However, the role of RhoA signaling in cardiac pathophysiology is poorly understood. To address this issue, we generated mice with cardiomyocyte-specific conditional expression of low levels of activated RhoA (CA-RhoA mice) and demonstrated that they exhibited no overt cardiomyopathy. When challenged by in vivo or ex vivo ischemia/reperfusion (I/R), however, the CA-RhoA mice exhibited strikingly increased tolerance to injury, which was manifest as reduced myocardial lactate dehydrogenase (LDH) release and infarct size and improved contractile function. PKD was robustly activated in CA-RhoA hearts. The cardioprotection afforded by RhoA was reversed by PKD inhibition. The hypothesis that activated RhoA and PKD serve protective physiological functions during I/R was supported by several lines of evidence. In WT mice, both RhoA and PKD were rapidly activated during I/R, and blocking PKD augmented I/R injury. In addition, cardiac-specific RhoA-knockout mice showed reduced PKD activation after I/R and strikingly decreased tolerance to I/R injury, as shown by increased infarct size and LDH release. Collectively, our findings provide strong support for the concept that RhoA signaling in adult cardiomyocytes promotes survival. They also reveal unexpected roles for PKD as a downstream mediator of RhoA and in cardioprotection against I/R.     

心肌缺血再灌注损伤的钙信号调节

目的:综合分析钙离子的调节机制及钙超载与心肌缺血再灌注损伤的关系。资料来源:应用计算机检索Pubmed1994-01/2004-01有关钙离子的调节机制及钙超载与心肌缺血再灌注损伤关系的文献,检索词“myocardialischemia/reperfusioninjury,calciumoverload”,并限定文章语言种类为English。同时计算机检索CNKI数据库1996-01/2004-04有关钙离子的调节机制及钙超载与心肌缺血再灌注损伤关系的文献,检索词“心肌缺血,再灌注损伤,钙超载”,限定文章语言种类为中文。资料选择:对检索到的钙离子调节机制及钙超载与心肌缺血再灌注损伤关系的相关信息进行整理,选取针对性强的文章,同一领域的文献则选择近期发表或权威杂志的文章。资料提炼:共检索到154篇相关文献,其中18篇文章符合要求。资料综合:①胞内钙离子浓度维持在一定范围时,细胞维持正常生理功能。当钙离子浓度升高,会发生一系列生理、生化反应,如细胞结构的损伤、凋亡、死亡和细胞的退行性改变等。②心肌缺血再灌注损伤与能量代谢障碍、氧自由基产生、钙超载等因素有关,但钙超载在缺血再灌注损伤中起极其重要的作用。结论:调节细胞内钙离子的动态平衡对维持细胞正常的生理功能和信息传递十分重要。钙超载是心肌缺血再灌注不可逆损伤的最后通路,但其具体作用途径有待于进一步研究。     

心肌缺血再灌注损伤的钙信号调节

目的：综合分析钙离子的调节机制及钙超载与心肌缺血再灌注损伤的关系。资料来源：应用计算机检索Pubmed 1994-01／2004-01有关钙离子的调节机制及钙超载与心肌缺血再灌注损伤关系的文献，检索词“myocardial ischemia／repemsion iniury，calcium overload”，并限定文章语言种类为English：同时计算机检索CNKI数据库1996-01／2004—04有关钙离子的调节机制及钙超载与心肌缺血再灌注损伤关系的文献，检索词“心肌缺血，再灌注损伤，钙超载”，限定文章语言种类为中文。 资料选择：对检索到的钙离子调节机制及钙超载与心肌缺血再灌注损伤关系的相关信息进行整理，选取针对性强的文章，同一领域的文献则选择近期发表或权威杂志的文章。 资料提炼：共检索到154篇相关文献，其中18篇文章符合要求。 资料综合：①胞内钙离子浓度维持在一定范围时，细胞维持正常生理功能。当钙离子浓度升高，会发生一系列生理、生化反应，如细胞结构的损伤、凋亡、死亡和细胞的退行性改变等。②心肌缺血再灌注损伤与能量代谢障碍、氧自由基产生、钙超载等因素有关，但钙超载在缺血再灌注损伤中起极其重要的作用。 结论：调节细胞内钙离子的动态平衡对维持细胞正常的生理功能和信息传递十分重要。钙超载是心肌缺血再灌注不可逆损伤的最后通路，但其具体作用途径有待于进一步研究。     

潘生丁预处理对大鼠肝缺血/再灌注损伤的保护作用

目的探讨潘生丁预处理对肝缺血／再灌注损伤的保护作用。方法 SD大鼠30只，随机分为假手术组、缺血／再灌注组及潘生丁组，每组10只。常温下制备大鼠肝缺血／再灌注损伤模型，潘生丁组于缺血前30min经门静脉给予潘生丁10mg／kg加生理盐水至0．5ml，假手术组和缺血／再灌注组注人等量生理盐水，用小号无损伤钳阻断肝门45min后恢复血流灌注，并于1h后取门静脉血测定血清丙氨酸转氨酶（ALT）、乳酸脱氢酶（LDH）、肿瘤坏死因子-α（TNF-Ⅱ）及内皮素-1（ET-1），同时取肝组织行病理组织学检查及腺苷酸含量测定。结果缺血／再灌注组血清ALT、LDH、TNF-α及ET-1均明显高于假手术组，潘生丁组则明显低于缺血／再灌注组（P均〈O．01）。缺血／再灌注组肝组织中腺苷酸含量明显低于假手术组，潘生丁组则明显高于缺血／再灌注组（P均〈O．01）。潘生丁组肝组织病理组织学改变明显轻于缺血／再灌注组，并接近假手术组。结论潘生丁预处理对肝缺血／再灌注损伤具有保护作用。     

Reversible acute myocardial injury following air bag deployment

This case report is about a 62 year old woman who was involved in an accident while driving her car, during which the driver side air bag deployed. She experienced intense anterior chest pain that radiated to her left arm after the accident, but was otherwise well; there was no significant medical history. An electrocardiogram done one and half hours after admission revealed 1 mm ST segment elevation in leads V2 and V3 and troponin 1 level was raised. She underwent cardiac catheterisation but three months after the accident both ECG and echocardiographic studies were normal. It is suggested that she underwent cardiac contusion rather than a myocardial infarction.     

Ischemic preconditioning protects against gut dysfunction and mucosal injury after ischemia/reperfusion injury

Mesenteric ischemia/reperfusion (IR) damages the gastrointestinal epithelia and impairs gut function. Ischemic preconditioning (IPC) has been shown to protect organs against IR injury. We hypothesized that IPC protects the gut from IR injury. Rats were randomized to a sham group, a sham early IPC + IR group (sham IPC + SMA occlusion for 30 min and 6 h of reperfusion), an early IPC + IR group (IPC, three cycles of SMA occlusion for 4 min and reperfusion for 10 min) followed immediately by SMA occlusion for 30 min and 6 h of reperfusion), a sham 24-h group, a sham late IPC + IR group (sham IPC followed by additional reperfusion for 24 h + SMA occlusion for 30 min and 6 h of reperfusion), and a late IPC + IR group (IPC protocol followed by additional reperfusion for 24 h, and then SMA occlusion for 30 min followed by 6 h of reperfusion). At 6 h, transit was determined and expressed as the mean geometric center. Ileum was harvested for assessment of mucosal injury and myeloperoxidase (MPO) activity. Tissue water was determined using the wet-to-dry weight ratio to assess gut edema. Early IPC + IR significantly improved transit (3.9 +/- 0.2), decreased MPO levels (3 +/- 2), and lessened mucosal injury (1.2 +/- 0.3) compared with animals subjected to sham early IPC + IR (transit, 2.9 +/- 0.2; MPO levels, 9 +/- 1; mucosal injury, 3.0 +/- 0.6). Late IPC + IR also improved transit (6.0 +/- 0.4) and decreased MPO levels (1 +/- 1) compared with sham late IPC + IR (transit, 4.4 +/- 0.2; MPO levels, 8 +/- 1), however, there was no difference in the mucosal protection between late IPC + IR (1 +/- 0.3) and sham late IPC + IR (1 +/- 1). Our results suggest that early and late IPC improves intestinal dysfunction, decreases inflammation, and provides mucosal protection in the intestine after IR. Our results show that IR-induced gut dysfunction can be improved by IPC. Both phases of IPC can potentially be useful in the clinical setting of surgical patient care.     

体外循环中西维来司钠对犬心肌缺血再灌注损伤的影响

目的探讨中性粒细胞弹性蛋白酶(NE)抑制剂西维来司钠对犬体外循环(CPB)中促炎性细胞因子IL-8和IL-1β引起的心肌缺血再灌注损伤的保护效果。方法将12只犬随机分为C组(n=6)和S组(n=6),建立CPB心肌缺血再灌注损伤模型。S组于CPB前静脉注射西维来司钠40 mg/kg,C组静脉注射等量生理盐水。分别于CPB前及转机后不同时点采集静脉血,检测炎性因子的浓度;于阻断前后分别取心肌标本进行丙二醛(MDA)和髓过氧化物酶(MPO)活性检测;于阻断前,开放30、60min测定血流动力学指标。结果阻断60min后,2组NE、IL-8和IL-1β浓度均显著升高(P<0.01);阻断60min及开放主动脉后,S组中性粒细胞数、NE、IL-8和IL-1β浓度显著低于C组(P<0.01);与C组比较,S组阻断60 min及开放主动脉60min时心肌组织匀浆MDA和MPO均显著降低(P<0.01),S组在开放主动脉30、60min时血流动力学指标恢复迅速(P<0.01)。结论 CPB中应用西维来司钠可明显减轻促炎性细胞因子和中性粒细胞介导的心肌缺血再灌注损伤。     

Hepatic injury and lipid peroxidation during ischemia and reperfusion

We determined the relationship between lipid peroxidation and alterations in hepatic secretory and microsomal function during various periods of hepatic ischemia/reperfusion. Rats were pretreated with alpha-tocopherol or vehicle and then subjected to 30, 60, and 90 min, no-flow hepatic ischemia in vivo with 1 or 5 h of reperfusion. Serum aminotransferase (ALT) level, wet-dry weight ratio, and lipid peroxidation were increased at 1 and 5 h of reperfusion, and these changes were significantly attenuated by alpha-tocopherol. Na+, K+-ATPase activity, and glucose-6-phosphatase activity were significantly decreased in 90-min ischemic rats, and these decreases were ameliorated by alpha-tocopherol. After 90 min of ischemia, bile flow, cholate output, and bilirubin output were markedly decreased by ischemia/reperfusion, and alpha-tocopherol restored the secretion. Cytochrome P450 content was decreased by ischemia/reperfusion and restored by alpha-tocopherol to the level of that found in the sham-operated group. Aminopyrine N-demethylase activity was decreased, and aniline p-hydroxylase was increased in 60-min ischemic rats. The changes in the activities of the two enzymes were prevented by alpha-tocopherol. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions and microsomal drug metabolizing systems in proportion to the duration of ischemia and reperfusion in vivo, and this is associated with increased lipid peroxidation.     

未成熟心肌缺血再灌注损伤后L-精氨酸的保护作用

目的:用幼兔体内心脏缺血再灌注损伤模型,研究小剂量L-精氨酸对未成熟心肌的保护效果。方法:24只新西兰幼兔(3～4周龄)随机分4组,每组6只:正常对照组;缺血/再灌注组;L-精氨酸组;L-硝基精氨酸甲酯组。测定各组的心室血液动力学指标、血浆肌酸激酶和乳酸脱氢酶(lactatedehydroge-nase,LDH)、心肌组织中总一氧化氮合酶(NOS)和诱导型一氧化氮合酶(iNOS)及eNOS(eNOS=总NOS-iNOS)活性。结果:L-精氨酸组左心室收缩压(LVSP)、心室内压力变化率(±dp/dt)、左心室舒张压(LVDP)恢复明显高于缺血/再灌注组和L-硝基精氨酸甲酯组(P<0.05);L-精氨酸组左心室舒张期末压(LVEDP)明显低于缺血/再灌注组和L-硝基精氨酸甲酯组(P<0.05)。L-精氨酸组的血浆肌酸激酶和LDH低于缺血/再灌注组和L-硝基精氨酸甲酯组(P<0.05)。缺血/再灌注组、L-精氨酸组、L-硝基精氨酸甲酯组总NOS高于正常对照组(P<0.05);L-精氨酸组eNOS高于正常对照组、缺血/再灌注组、L-硝基精氨酸甲酯组(P<0.05)。4组iNOS差异无显著性意义(P>0.05)。结论:小剂量L-精氨酸能改善缺血/再灌注损伤后未成熟心肌的左心室血流动力学指标,这种保护作用是通过提高eNOS活性实现的,而与iNOS活性无关。     

内洋地黄素拮抗剂减轻心肌缺血再灌注损伤的实验研究

目的 观察心肌缺血再灌注(myocardial isehemia reperfusion，MIR)时心肌组织内洋地黄素水平的变化和内洋地黄索特异性拮抗剂地高辛抗血清对MIR的影响，证明内洋地黄素是介导MIR损伤的重要介质之一。方法 采用左冠状动脉前降支结扎30min，复灌45min建立在体大鼠MIR、模型。SD大鼠随机分成7组：假手术组，模型组，生理盐水组，维拉帕米组，小剂量、中剂量、大剂量地高辛抗血清组。连续记录Ⅱ导联心电图，于再灌注45min后立即取左室心尖部缺血区心肌，检测心肌匀浆中内洋地黄素含量、心肌细胞膜Na^ -K^ -ATP酶和线粒体内Ca^2 含量。结果MiR损伤时，心肌组织内洋地黄素水平明显升高。心肌细胞膜Na^ -K^ -ATP酶活性显著下降，线粒体内Ca^2 含量升高；心电图ST段显著抬高，再灌注时发生明显的室性心律失常。地高辛抗血清组可显著降低心肌组织内洋地黄素水平，恢复细胞膜Na^ -K^ -ATP酶活性，降低线粒体内Ca^2 含量；显著改善MIR所致ST段抬高和再灌注心律失常的发生率。结论 MIR时，心肌组织内洋地黄素水平显著升高，是介导MIR损伤的重要物质之一。地高辛抗血清通过拮抗内洋地黄素的生物学作用，减轻MIR损伤。