3,4,5,6-Tetrahydroxyxanthone Protects Against Myocardial Ischemia-Reperfusion Injury in Rats

In the present study, we tested the protective effect of 3,4,5,6-tetrahydroxyxanthone, a synthetic xanthone derivative, on myocardial ischemia-reperfusion injury in rats. Ischemia-reperfusion injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts or 30 min coronary artery occlusion and 120 min reperfusion in vivo, respectively. Heart rate, coronary flow (CF), left ventricular pressure (LVP), and its first derivative (+/- dp/dt (max)) were recorded, and the activity of creatine kinase in coronary effluent and tumor necrosis factor-alpha (TNF-alpha) content in myocardial tissues were measured in vitro. The activity of serum creatine kinase, the level of TNF-alpha and interleukin-6 (IL-6), and myocardial infarct size were measured in vivo. 3,4,5,6-tetrahydroxyxanthone (30, 100 or 300 microM) caused a significant improvement of cardiac function (LVP and +/- dp/dt (max)) and a decrease in the release of creatine kinase in coronary effluent as well as the level of TNF-alpha in myocardial tissues in vitro. 3,4,5,6-tetrahydroxyxanthone (0.5 or 1.0 mg/kg, i.v.) also markedly decreased infarct size and the release of creatine kinase and TNF-alpha, and increased serum IL-6 level in vivo. These results suggest that 3,4,5,6-tetrahydroxyxanthone possesses a protective effect on myocardial ischemia-reperfusion injury, and that the protective effects of 3,4,5,6-tetrahydroxyxanthone may be related to inhibition of TNF-alpha production and stimulation of IL-6 generation by inhibition of ROS production.     

Sepsis Protects the Heart of Alcoholic Rats from Ischemia-Reperfusion Injury

We have previously shown that administration of Escherichia coli to a rat induces cardiac dysfunction, but also prevents the myocardium from being further damaged by total ischemia. We have also previously shown that induction of sepsis in a rat that has consumed alcohol as 36% of its caloric intake for 8–10 weeks, results in a potentiation of the cardiac depression resulting from sepsis. In this study, we determined if administration of Gram-negative bacteria to a chronically alcoholic rat would still protect the heart from ischemia-reperfusion injury. We tested the protective effect of sepsis using an in vitro, isovolumically contracting heart preparation. Global ischemia was maintained for 35 min, followed by 25-min reperfusion. In the present experiments, sepsis produced a 40% decrease in cardiac performance, but was also protective of hearts made ischemic the next day. Hearts from septic and alcoholic septic rats recovered 100% of preischemic ventricular function after 35-min ischemia, whereas hearts from the control and alcohol groups recovered only 80% of preischemic left ventricular performance. Whereas preischemic function was significantly decreased in the septic groups compared with the two nonseptic groups, postishemic function was no longer significantly different in the four groups. Thus, sepsis resulted in development of protection of the hearts from ischemia-reperfusion injury, even in hearts that were severely compromised by the combination of chronic alcoholism and Gram-negative sepsis.     

Role of the Sodium-Hydrogen Exchanger in Ischemia-Reperfusion Injury in Diabetes

Ischemic heart disease is a significant problem in the diabetic population. Animal models of diabetes show a paradoxical resistance to ischemic challenge. The present treatise will discuss the mechanics involved and the central role that Na+-H+ exchanger plays in this response to ischemic-reperfusion injury.     

Mitochondrial Homeostasis and Mast Cells in Experimental Hepatic Ischemia-Reperfusion Injury of Rats

Background:Ischemia-reperfusion injury is a histopathological event and is an important cause of morbidity and mortality after hepatobiliary surgery. We aimed to investigate the protective effect of uridine on hepatic ischemia-reperfusion injury in rats.Methods:he animals were divided into 4 groups (n = 8): group I (control), group II: ischemia-reperfusion (30 minutes ischemia and 120 minutes reperfusion), group III: ischemia-reperfusion + uridine (at the beginning of reperfusion), and group IV: ischemia-reperfusion + uridine (5 minutes before ischemia-reperfusion). Uridine was administered a single dose of 30 mg/kg IV. The 3 elements of the hepatoduodenal ligament (hepatic artery, portal vein, and biliary tract) were obliterated for 30 minutes. Then hepatic reperfusion was achieved for 120 minutes.Results:In the ischemia-reperfusion group, both liver tissues and serum chymase activity and high-temperature requirement A2 levels were higher. Severe central vein dilatation and congestion, widening sinusoidal range, diffuse necrotic hepatocytes and dense erythrocyte accumulation in sinusoids, and strongly inducible nitric oxide synthase expression were seen in the ischemia-reperfusion group. A clear improvement was seen in both uridine co-administration and pretreatment groups.Conclusion:Our results revealed that uridine limits the development of liver damage under conditions of ischemia-reperfusion, thus contributing to an increase in hepatocyte viability.     

Antihypertensive Action of Melatonin in the Spontaneously Hypertensive Rat

The effects of melatonin on blood pressure and heart rate were studied in 23-week-old male spontaneously hypertensive rats. Melatonin infused i.p. at a dose of 6 mg/rat per day for 5 days using an osmotic minipump produced a significant reduction of blood pressure and a slight but significant decrease of heart rate in the conscious and unrestrained state. These cardiovascular effects of melatonin developed gradually. Plasma renin concentration tended to decrease after melatonin treatment. These results demonstrate that melatonin has an antihypertensive action. The mechanism of the antihypertensive action of melatonin requires further study.     

Melatonin in Serum and the Pineal of Spontaneously Hypertensive Rats

Involvement of melatonin in the blood pressure regulation as an endogenous central hypotensive factor has been suggested in rats and in man. We studied the relationship between melatonin and the development of hypertension in 5- and 15-week-old spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats, by measuring serum and the pineal concentrations with a sensitive and specific radioimmunoassay coupled with a novel extraction method. Serum melatonin concentration at midnight in young SHR rats was significantly higher than that in age-matched WKY rats (P < 0.01), whereas it was decreased in the adult SHR (P < 0.01). No such differences were observed at noon. Pineal content of melatonin at midnight in 5-week-old SHR rats was lower than in age-matched WKY rats (P < 0.01). These data demonstrate that melatonin in the nocturnal serum of SHR rats is elevated at prehypertensive stage while it is decreased after the development of hypertension. The role of melatonin in the hypertensive process in SHR rats requires further study.     

肾血管性高血压大鼠心脏肥厚不同时期血浆及组织心钠素、内皮素含量变化

目的 了解高血压心脏病左室结构、功能变化时血浆及心肌组织中心钠素(atrial natriuretic peptide ANP)、内皮素(endothelin ET)含量变化。方法 应用放免法监测二肾一夹意义型(2K1C)肾血管性高血压大鼠(RHR)血浆及心肌组织中ANP、ET含量变化，并根据超声心动图评价高血压大鼠心脏结构、功能动态变化，将高血压大鼠进行分组。结果 高血压左室向心性肥厚期血浆及心肌组织(左心室)中ANP、ET含量明显升高；左室离心性肥厚期血浆ET较向心性肥厚期组更高，但心肌组织中ET含量与其无显著差别，而血浆及心肌组织中．ANP含量均较向心性肥厚期组低。结论 2K1C型高血压大鼠血浆及心肌组织中ANP、ET含量均升高；血浆ET与．ANP含量变化在左室肥厚中可能起着更为重要作用。     

Melatonin protects against pro-oxidant enzymes and reduces lipid peroxidation in distinct membranes induced by the hydroxyl and ascorbyl radicals and by peroxynitrite

We have investigated the action of melatonin against lipid peroxidation in membranes including brain homogenates (BH), brain and liver microsomes (MIC), and phosphatidylcholine (PC) liposomes, as well as its effect on the activity of pro-oxidant enzymes such as constitutive neuronal nitric oxide synthase (cnNOS), xanthine oxidase (XO) and myeloperoxidase (MPO). The liposomes were reconstituted by a dialysis method, lipid peroxidation was monitored using the thiobarbituric reactive substances (TBARS) method and enzyme activities were measured spectrophotometrically. The ascorbyl and hydroxyl free radicals were generated by the reaction of ascorbic acid + FeSO4 and H2O2 + FeCl2, respectively, and peroxynitrite using a mixture of NaNO2 in an alkaline medium. Melatonin protected against lipid peroxidation induced by distinct reactive oxygen species (ROS) in all membranes tested although with different potency, in the following order BH < MIC < PC. The K0.5 for enzyme inhibition by melatonin was determined for nNOS (2.0 +/- 0.1 mm), for XO (0.8 +/- 0.1 mm) and for MPO (0.063 +/- 0.003 mm), the latter one with high affinity. Melatonin showed a weak effect as a nitrogen monoxide (NO) scavenger in the presence of sodium nitroprusside (NO donor) and low reactivity with 1,1-diphenyl-2-picryl hydrazyl (DPPH). These results demonstrate the antioxidant action of melatonin, principally that related to the activity of pro-oxidant enzymes such as XO and MPO.     

Isolated Heart Function after Ischemia and Reperfusion in Sucrose-Fed Rats: Influence of Gender and Treatment

Sucrose-fed rats (HTG) develop hypertension, hypertriglyceridemia, and other features of the metabolic syndrome. This condition, nowadays a world epidemic, is more prevalent in males and increases the risk of cardiovascular diseases. Weanling male and female rats were given either tap water in control (C) or 30% sucrose solution in HTG groups and commercial rat chow for 3, 5, or 8 months. We studied possible variations in cardiac function, due to gender and length of treatment, in isolated heart after ischemia-reperfusion, since an impaired performance may be more easily detected under stress. Together, sucrose treatment and age affected all cardiac variables. Gender had significant effect on coronary vascular resistance and postischemic levels of the enzyme CK-MB; the percentages of retained cardiac enzymes after ischemia were higher in C and HTG females. C and HTG males had a higher incidence of arrhythmias than females, but only HTG males suffered lethal ventricular fibrillation.     

Protective Effect of Melatonin on Renal Injury of Rats Induced by Bile Duct Ligation

Oxygen radicals have been implicated in the pathogenesis of renal injury induced by extrahepatic cholestasis. We conduct this study to investigate whether melatonin can have a protective effect against such injury. Either normal saline or gentamicin with or without melatonin was injected into rats that received either a bile duct ligation or a sham operation. The serum levels of malondialdehyde and total antioxidative activity were measured. The kidney was fixed for histologic scoring of renal injury. The serum malondialdehyde level was highest in the rats that received both bile duct ligation and gentamicin injection. Treatment with melatonin significantly increased the serum total antioxidative activity and reduced the serum malondialdehyde concentration. The mean score of renal injury, highest in the rats receiving bile duct ligation and gentamicin injection, was significantly reduced with melatonin treatment. By reducing the systemic oxygen radicals, supplementation with antioxidants exerts a protective effect on the renal injury induced by extrahepatic cholestasis.     

mitoKATP通道在瑞舒伐他汀联合缺血后处理减轻糖尿病大鼠心肌缺血再灌注损伤中的作用

目的观察瑞舒伐他汀后处理联合缺血后处理是否能减轻2型糖尿病大鼠缺血再灌注损伤并探讨其相应机制。方法建立2型糖尿病大鼠模型,并随机分成7组(每组9只):假手术组、缺血再灌注损伤组(IRI组)、瑞舒伐他汀后处理+缺血后处理组(RPO+IPO组)、瑞舒伐他汀后处理+缺血后处理组+5-羟基喹酸盐组(5-HD组)、瑞舒伐他汀后处理+缺血后处理组+二氮嗪组(二氮嗪组)、瑞舒伐他汀后处理+缺血后处理组+HMR-1098组(HMR-1098组)、瑞舒伐他汀后处理+缺血后处理组+克罗卡林组(克罗卡林组)。进行45 min缺血和120 min再灌注,观察心肌梗死区面积及心肌细胞线粒体超微结构和血清心肌肌钙蛋白T水平。结果 RPO+IPO组、二氮嗪组、HMR-1098组和克罗卡林组心肌梗死面积较IRI组明显减小(P<0.05),5-HD组心肌梗死面积明显大于RPO+IPO组、二氮嗪组、HMR-1098组及克罗卡林组(P<0.05)。IRI组和5-HD组心肌细胞线粒体超微结构损伤重,RPO+IPO组、二氮嗪组、HMR-1098组及克罗卡林组心肌细胞线粒体超微结构基本完整。RPO+IPO组、二氮嗪组、HMR-1098组及克罗卡林组血清心肌肌钙蛋白T水平较IRI组明显减少(P<0.05),5-HD组血清心肌肌钙蛋白T水平与IRI组无明显差异,但明显高于RPO+IPO组、二氮嗪组、HMR-1098组及克罗卡林组(P<0.05)。结论瑞舒伐他汀后处理联合缺血后处理可明显减轻2型糖尿病大鼠缺血再灌注损伤,mitoKATP通道开放在此作用中起主导地位。     

Effects of Melatonin on Ischemia and Reperfusion Injury of the Rat Heart

Effects of melatonin on various manifestations of ischemia/reperfusion injury of the isolated perfused rat heart were examined. Ischemia- and reperfusion-induced ventricular arrhythmias were studied under constant flow in hearts subjected to 10, 15 or 25 min of regional ischemia (induced by LAD coronary artery occlusion) and 10-min reperfusion. Melatonin was added to the perfusion medium 5 min before ischemia at concentrations of 10 mol/l or 10 nmol/l and was present throughout the experiment. Recovery of the contractile function was evaluated under constant perfusion pressure after 20-min global ischemia followed by 40-min reperfusion. Hearts were treated with melatonin at a high concentration (10 mol/l) either 5 min before ischemia only (M1) or 5 min before ischemia and during reperfusion (M2) or only during reperfusion (M3). At the high concentration, melatonin significantly reduced the incidence of reperfusion-induced ventricular fibrillation and decreased arrhythmia score (10% and 2.2 ± 0.3, respectively) as compared with the corresponding untreated group (62% and 4.1 ± 0.3, respectively); the low concentration had no effect. This substance did not affect the incidence and severity of ischemic arrhythmias. Melatonin (M2, M3) significantly improved the recovery of the contractile function as compared with the untreated group; this protection did not appear if melatonin was absent in the medium during reperfusion (M1). Our results show that melatonin, in accordance with its potent antioxidant properties, effectively protects the rat heart against injury associated with reperfusion. It appears unlikely that melatonin is cardioprotective at physiological concentrations.     

自发性高血压大鼠心肌fas基因表达与左室肥厚关系探讨

目的 探讨自发性高血压大鼠（SHR）心肌fas表达及其与左室肥厚的关系。方法 自发性高血压大鼠（SHR）与正常血压大鼠各16号，尾套法测收缩压，逆转录-聚合酶边反应（RT-PCR）法测心肌fas mRNA表达。结果 与WKY相比，SHR心肌fas表达、左室重量指数(LVMI)均显著升高，且二者呈正相关。结论 自发性高血压大鼠早期心肌肥厚时心肌fas表达已经升高，可能参与后期心衰的发生。     

Effect of Losartan on Right Ventricular Hypertrophy and Cardiac Angiotensin I-Converting Enzyme Activity in Pulmonary Hypertensive Rats

The aim of this study was to investigate the effect of prophylactic treatment with the angiotensin type 1 (AT₁) receptor antagonist losartan on right ventricularhypertrophy and cardiac angiotensin I-converting enzyme (ACE) activity in a rat model of monocrotaline-induced pulmonary hypertension. Losartan failed to prevent either pulmonary hypertension or right ventricular hypertrophy. Right ventricular ACE in untreated pulmonary hypertensive rats did not differ from control rats. Losartan treatment in pulmonary hypertensive rats caused a significant 2-fold increase of ACE activity in the hypertrophied right (p<0.005) but not in the left ventricle. Thus, cardiac ACE activity is not stimulated in rats with monocrotaline-induced right ventricular hypertrophy. Prophylactic losartan treatment in this model of progressive pulmonary hypertension failed to prevent or reduce the increase in ventricular afterload. The relevance of the increase in right ventricular ACE activity during pulmonary hypertension after losartan treatment is unknown and needs to be evaluated in further studies.     

Acceleration of Hypertensive Cerebral Injury by the Inhibition of Xanthine-Xanthine Oxidase System in Stroke-Prone Spontaneously Hypertensive Rats

It is well-known that, in ischemic cerebral injury, a free radical and its byproducts are generated by xanthine-xanthine oxidase system and eliminated by scavengers such as superoxide dismutase (SOD), catalase, uric acid and ascorbic acid. To investigate the possible involvement of the xanthine-xanthine oxidase system in hypertensive cerebral injury, we examined chronological changes in uric acid level in the cerebral cortex and the effects of the inhibition of xanthine oxidase or catalase using stroke-prone spontaneously hypertensive rats (SHRSP).     

天麻钩藤饮对腹主动脉狭窄-高盐型高血压大鼠血压等因素的影响

目的 观察天麻钩藤饮对腹主动脉狭窄-高盐型高血压大鼠血压等因素的影响.方法 将25只SD大鼠随机分为假手术组、实验性高血压组、实验性高血压天麻钩藤饮灌胃组.用手术和高盐饲养的方法制成腹主动脉狭窄-高盐摄入型高血压大鼠,在制备高血压病理模型的同时,用药组每天用天麻钩藤饮灌胃,观察30 d后对大鼠血压、心率及心指数的影响.结果 30 d后,高血压病理模型未用药组与假手术组比较血压明显升高,心率加快,心指数增加,均有统计学意义(P<0.05);高血压病理模型用药组与未用药组比较血压减低,心率减慢,心指数减少,均有统计学意义(P<0.05).结论 天麻钩藤饮可降低腹主动脉狭窄-高盐型高血压大鼠的血压、心率及心指数.     

中药对脑缺血再灌注损伤保护的研究进展

综述中药对脑缺血再灌注损伤的保护作用，为临床防治缺血再灌注损伤提供一定的理论依据。     

黄龙通络胶囊对大鼠心肌缺血再灌注心律失常的影响

目的探索黄龙通络胶囊对心肌缺血再灌注所致大鼠心律失常模型的保护作用。方法采用结扎大鼠冠状动脉前降支,引起心肌缺血再灌注所致心律失常模型,记录各组大鼠Ⅱ导联心电图,并测定心肌组织中Na+-K+-ATPase、Ca2+-Mg2+-ATPase的活性。结果黄龙通络胶囊有稳定QRS间期、PR间期的作用,能降低抬高的ST段;能显著提高线粒体膜Na+-K+-ATPase、Ca2+-Mg2+-ATPase活性。结论黄龙通络胶囊可能是通过保持缺血-再灌注心肌细胞膜的稳定性,改善缺血心肌能量代谢障碍,而发挥其抗心律失常的作用。