缬沙坦对心肌缺血再灌注损伤的保护作用

目的 用兔在体心肌缺血再灌注模型研究缬沙坦(valsartan)后处理对缺血再灌注心肌的保护作用及其机制.方法 兔24只,随机分为3组,对照组:结扎冠状动脉前降支1 h,再灌注5 h;后处理组:处理同对照组外,于再灌注前15 min耳缘静脉注射缬沙坦,剂量30 mg/kg;缬沙坦组:处理同后处理组外,在再灌注前5 min耳缘静脉注射磷酸肌醇3激酶抑制剂LY294002(0.3 mg/kg).分别于再灌注3 h和5 h取兔血,测定各组血超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛的水平.实验终末,取结扎部位心肌进行免疫组化处理,观察心肌组织蛋白激酶B和内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)含量以及心肌组织结构的变化.结果 后处理组血SOD含量高于其它组(P＜0.01),丙二醛含量低于其它组(P＜0.01),后处理组心肌组织蛋白激酶B和eNOS含量明显高于其它组(P＜0.01);其余组间各项观察指标无显著差异.结论 缬沙坦后处理对缺血再灌注心肌具有保护作用,其作用可能是通过再灌注损伤清除激酶信号转导通路来实现的.     

心肌缺血再灌注损伤与钙通道阻滞剂的保护作用

随着药物血栓溶解疗法与外科冠状动脉搭桥术的日臻完善,心肌梗塞的死亡率明显下降,为此患者的预后问题受到医学界广泛重视。同时如何正确地评介再灌注对缺血心肌的影响以及如何最大效率地减轻心肌缺血再灌注损伤已成为临床医学界令人注目的课题,亟待解决。随着Hearse氏氧矛盾的发现,加深了对再灌注的认识与了解,同时也推动了临床心肌梗塞有效防治措施的实     

小檗胺对大鼠心肌缺血再灌注损伤的保护作用机制

用离体大鼠心脏制成心肌缺血模型，缺血４０分种后再灌注２０分种，心功能明显减弱，肌酸激酶（ＣＫ）释放增加，心肌Ｎａ，Ｋ－ＡＴＰ酶活性受到抑制。缺血４０分钟后心肌Ｎａ＾＋含量增加，Ｋ＾＋含量降低，再灌注后Ｃａ＾２＋含量显著增加。小檗胺可明显改善心功能，降低室颤发生率，减少再灌注后ＣＫ的释放，保持再灌注时Ｎａ，Ｋ－ＡＴＰ酶活性，减少缺血和再灌注Ｎａ＾＋和Ｃａ＾２＋含量的增加。另外，采有低温电子自旋共振技     

褪黑素对心肌缺血再灌注损伤的保护作用

目的　探讨褪黑素增补于停搏液中对缺血再灌注离体鼠心的保护作用。方法　将 2 4只 Wistar大鼠随机分为褪黑素组 (A )和对照组 (B)。离体鼠心在改良的 L angendorff- Neely灌注模型上 30分钟预灌注 ,12 0分钟停搏 ,30分钟再灌注。缺血前及再灌注期间测定血流动力学指标、心肌酶 (包括 CPK、L DH)、心肌超氧化物歧化酶 (SOD)、过氧化脂质 (L PO)含量。电镜观察心肌超微结构。结果　再灌注后 ,A组心功能、心肌超微结构的改善明显优于 B组 ;心肌酶 (CPK,L DH)、过氧化脂质 (L PO)含量显著低于 B组 (P<0 .0 1) ;心肌超氧化物歧化酶 (SOD)含量显著高于 B组 (P<0 .0 1)。结论　褪黑素增补于停搏液中可显著减轻心肌缺血再灌注损伤 ,具有良好的心肌保护作用     

一氧化氮在心肌缺血再灌注损伤中的作用

90年代以来,人们对一氧化氮(ＮｉｔｒｉｃＯｘｉｄｅ,ＮＯ)在心肌缺血再灌注过程中的作用进行了大量研究,结论不甚一致,争论的焦点集中在以下两个方面:1在心肌缺血再灌注过程中,ＮＯ的产生是增加还是减少?2ＮＯ是参与了心肌缺血再灌注损伤,还是减轻心肌缺血再灌注损伤。本文对近年来有关ＮＯ与心肌缺血再灌注损伤的实验进行了分析和总结,旨在澄清ＮＯ在心肌缺血再灌注过程中的作用。一、ＮＯ的产生与心肌缺血再灌注　心肌缺血再灌注过程中ＮＯ的产生量,不同的实验有不同的结论。Ｔｓａｏ等[1]在猫局部心肌缺血90ｍｉｎ后再灌注实验中,发现再…     

黄芪甲苷灌胃预处理对大鼠心肌缺血再灌注损伤的保护作用

目的探讨黄芪甲苷灌胃预处理对大鼠心肌缺血再灌注损伤(I/R)的保护作用。方法将100只大鼠随机分为三组,最终90只大鼠造模成功,其中假手术组29只,模型组30只,干预组31只。假手术组与模型组给予普通饲养+生理盐水(2 ml·kg-1·d-1)灌胃,干预组给予普通饲养+黄芪甲苷(10 mg·kg-1·d-1)灌胃。造模时,假手术组大鼠只在冠状动脉左室支左心耳下缘约0.5 cm处穿线,不结扎;模型组及干预组大鼠给予结扎。于灌注24 h后采用TUNEL法计算细胞凋亡指数(AI),比较Bax、Bcl-2以及半胱氨酸蛋白酶(caspase)-3蛋白的表达。结果三组间AI、Bax、Bcl-2以及caspase-3蛋白比较差异表达(均P0.05),进一步两两比较,模型组及干预组的AI、Bax、Bcl-2以及caspase-3蛋白的表达显著高于假手术组,模型组的AI、Bax、caspase-3蛋白表达显著高于干预组,Bcl-2蛋白表达显著低于干预组(均P0.05)。结论在大鼠心肌缺血再灌注过程中存在明显的细胞凋亡过程,在此过程中,黄芪甲苷可能通过上调Bcl-2的表达、降低Bax的表达实现其对心肌细胞的保护作用。     

苯那普利对离体大鼠缺血再灌注心肌的保护作用

目的观察苯那普利对离体大鼠缺血再灌注心肌的保护作用,初步探讨其作用机制。方法应用Langendorff装置,采用完全停灌复灌的方法制作离体大鼠心肌缺血再灌注模型。将24只SD大鼠随机等分3组:对照组(KH液持续灌注110 min),缺血再灌注组(KH液灌流20 min,停灌30 min,再灌注60 min),苯那普利组(缺血30 min,再灌注60 min,灌注液加入苯那普利10-6mol/L)。观察再灌注心律失常发生情况、血流动力学、光镜下心肌结构改变、心肌肿瘤坏死因子-α(TNF-α)免疫组织化学染色。结果与缺血再灌注组比,苯那普利组再灌注60 min内室性心动过速、心室颤动发生率降低;血流动力学指标明显改善;光镜可见炎症损伤减轻。免疫组织化学染色可见TNF-α蛋白阳性表达主要在心肌细胞胞浆苯那普利组呈弱阳性;对照组阴性;缺血再灌注组强阳性。结论苯那普利对缺血再灌注心肌具有保护作用,其机制可能与抑制TNF-α表达、减轻炎症有关。     

Protective effects of gradual restoring of calcium on working rat hearts with ischemia-reperfusion injury]

The effects of gradually restoring calcium concentration in initiating reperfusion on cardiac function, coronary blood flow and myocardial calcium content during reperfusion following global ischemia have been observed in isolated working rat hearts. The results showed that gradually restoring calcium reperfusion facilitated the recovery of the contracting relaxing and pump functions as well as coronary blood flow, and decreased the occurrence of arrhythmias during reperfusion and myocardial calcium content after reperfusion. The mechanism of the protective effect of gradual calcium restoration on the hearts was probably due to the inhibition of calcium overload in cardiac cells. However high calcium reperfusion deteriorated cardiac function.     

Protective effects of regulatory amino acids on ischemia-reperfusion injury in the isolated perfused rat liver

OBJECTIVE: Some amino acids (AAs) display potent regulatory activities on cell metabolism, including via anti-oxidative defences. The aim of this study was to evaluate the protective effect of these AAs on warm ischaemia-reperfusion (I/R) injury in the isolated perfused rat liver. MATERIAL AND METHODS: Livers from fasted male Sprague-Dawley rats were isolated and perfused without (control group) or with (AP group) a mixture of regulatory AAs (glutamine, histidine, leucine, methionine, proline, phenylalanine, tryptophan and alanine). After 45 min of perfusion, warm ischaemia was induced for 45 min by clamping the portal vein catheter; thereafter, reperfusion was performed for 30 min. RESULTS: TNF-alpha production was significantly lower in the AP group during reperfusion (Control: 39+/-7 versus AP: 16+/-2 pg min-1 g-1, p<0.05), and lactate dehydrogenase (LDH) release decreased significantly during the last 15 min of reperfusion (Control: 0.13+/-0.03 versus AP: 0.04+/-0.02 IU min-1 g-1, p<0.05), despite similar levels of oxidative stress. The addition of regulatory AAs was not associated with variations in portal flow, bile flow, hepatic glucose or urea metabolism. However, significant changes in intrahepatic glutamine (Control: 1.4+/-0.2 versus AP: 2.6+/-0.5 micromol g-1, p < 0.05) together with higher glutamate release in the AP group (Control: 10.2+/-5.4 versus AP: 42.6+/-10.9 nmol min-1 g-1, p < 0.05) indicated modifications in nitrogen metabolism. CONCLUSIONS: Taken together, the lower TNF-alpha production, suggesting decreased inflammatory response, the decrease in LDH release in the AP group, demonstrating a better preservation of liver viability, and the increase in hepatic glutamine indicate that AAs play an important role in the liver's response to I/R.     

金属硫蛋白对离体心脏心肌间质的保护作用

目的 探讨金属硫蛋白(MT)对离体心脏心肌间质的影响。方法 Wistar大鼠16只,分为2组:对照组(C,n=8),腹腔注射蒸馏水0.5ml 24h后取离体心脏行离体灌注(Langendorff模型),测定心功能,然后灌注HTK心脏保护液,4C保存3h后再行Langendorff灌注25min;实验组(E,n=8)腹腔注射3.6％硫酸锌(1.5 ml/kg)24 h后取离体心脏,处理方法同C组。以心肌细胞中MT含量、血流动力学指标、心肌组织羟脯氨酸(HP)含量、内皮素(ET)含量和心肌超微结构等作为观察指标。结果MT含量E组与C组比较明显增高;E组心功能恢复方面优于C组(P<0.05),HP含量优于C组(P<0.01),ET含量低于C组(P<0.01),心肌超微结构损伤较C组明显减轻。结论MT对供心心肌间质具有保护作用。     

Adenosine deaminase inhibitor (EHNA) on ischemia-reperfusion injury in isolated perfused rat hearts

The effects of Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) on Langendorff perfused rat hearts subjected to ischemia-reperfusion injury were studied. Results showed that EHNA can inhibit the increase of cardiac resting tension during ischemia period and decreasing the incidence of ventricular fibrillation and its duration. The contraction amplitude, resting tension and heart rate could be recovered to preischemic level, and the coronary flow even greater than before. The authors thought that EHNA can block the breakdown of adenosine to inosine and hypothanxine, and, therefore, cut off the pathway and production of oxygen free radicals during ischemia-reperfusion injury.     

Protective effects of ischemic postconditioning against hypoxia-reoxygenation injury and hydrogen peroxide-induced damage in isolated rat hearts

OBJECTIVE: Ischemic preconditioning (PR) protects hearts from ischemia-reperfusion injury. The purpose of the present study was to examine the protective effect of PR and postconditioning (PT) against hypoxia-reoxygenation injury and H(2)O(2)-induced damage in isolated rat hearts. METHODS AND RESULTS: Hearts from male Sprague-Dawley rats were perfused with Krebs-Henseleit solution by Langendorff methods and subjected to two protocols. In protocol A, control hearts underwent 45 min of hypoxia and 30 min of reoxygenation. Three PT cycles of 10 s of ischemia and 10 s of reperfusion after 45 min of hypoxia increased the recovery of the pressure-rate product. Three PR cycles of 3 min of ischemia and 5 min of reperfusion before hypoxia were also protective, and decreased the release of glutamic oxaloacetic transaminase. A combination of PR and PT resulted in greater protection than either alone. In protocol B, control hearts underwent perfusion with H(2)O(2) (120 muM) until the left ventricular end-diastolic pressure was elevated to 50 mmHg, and then H(2)O(2) was washed out for 30 min. Three PT cycles of 30 s of ischemia and 30 s of reperfusion before the 30 min washout increased the level of recovery of the pressure-rate product and decreased left ventricular end-diastolic pressure to baseline levels. CONCLUSIONS: The results of the present study indicate that PT protects hearts from hypoxia-reoxygenation injury and H(2)O(2)-induced damage. In addition, PR combined with PT offers more effective protection than PR or PT alone.     

白藜芦醇预处理对体外大鼠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体外大鼠缺血再灌注心肌损伤的保护作用及其作用机制。方法:利用Langendorff灌注系统,建立体外大鼠心肌常温全心心肌缺血30min再灌注120min损伤模型。将56只雄性SD大鼠随机分为4组(每组14只):缺血再灌注损伤(IRI)组、白藜芦醇组、Nω硝基L精氨酸甲酯(LNAME)组、氨基胍(AG)组。检测各组的心功能、心肌一氧化氮合酶(NOS)同工酶(NOSi)活性、一氧化氮(NO)的含量、丙二醛的含量、心肌梗死面积以及心肌细胞凋亡指数。结果:与IRI组相比,白藜芦醇组左室发展压(LVDP)、左室压力上升和下降最大变化速率(±dp/dtmax)明显改善(P<0.05或0.01);心肌梗死面积、心肌细胞凋亡指数、心肌丙二醛含量显著降低(P<0.01);心肌NOSi活性和NO含量显著升高(P<0.01)。LNAME组和AG组LVDP和±dp/dtmax显著低于白藜芦醇组(P<0.05或P<0.01);心肌梗死面积、心肌细胞凋亡指数、心肌丙二醛含量显著升高(P<0.01);心肌NOSi活性和NO含量显著降低(P<0.01)。结论:白藜芦醇对体外大鼠IRI具有保护作用,其机制可通过提高心肌NOSi活性,促进NO产生而介导的。     

The dual effects of nitric oxide synthase inhibitors on ischemia-reperfusion injury in rat hearts

Objective Nitric oxide (NO) is known to act as a mediator of tissue injury as well as being a potent endogenous vasodilator. The functional and metabolic effects of NO on ischemia-reperfusion injury are still controversial. The aim of this study was to clarify the relationship between the degree of NO synthase (NOS) inhibition and the effects on ischemia-reperfusion injury.Methods and results Langendorff-perfused rat hearts were subjected to 30 minutes of global ischemia followed by 30 minutes of reperfusion. The recovery of left ventricular developed pressure (LVDP), creatine kinase (CK) release, and myocardial high energy phosphates were measured in hearts perfused with or without NOS inhibitors, L-N^G-monomethyl arginine (L-NMMA) or N^Gnitro-L-arginine methylester (L-NAME). NOS inhibitors exerted different effects on the recovery of LVDP and CK release depending on the concentration. The low dose of L-NMMA improved the recovery of LVDP, decreased the CK release during reperfusion, and preserved the myocardial adenosine triphosphate content after reperfusion. In contrast, the high dose of L-NMMA had adverse effects. L-NMMA reduced NO release in coronary efuent in a dose-dependent fashion. Both effects of L-NMMA were abolished by excessive co-administration of L-arginine and the same doses of D-N^G-monomethyl arginine (D-NMMA) showed no effect on ischemia-reperfusion injury. Therefore, both effects were due to NOS inhibition. In addition, L-NMMA suppressed the myocardial malondialdehyde accumulation, an indicator of oxidative stress, which might be attributed to the beneficial effects by partial NOS inhibition. On the other hand, the high dose L-NMMA signicantly decreased coronary ow during aerobic perfusion and reperfusion. Therefore, it is conceivable that the vasoactive NOS inhibition contributes to the harmful effects, which might exceed the benecial effects due to a decrease in oxidative stress.Conclusion The present results showed that NO inhibitors had dual effects on mechanical function and energy metabolism depending on the concentration. Non-vasoactive inhibition of NOS had benecial effects due to the suppression of oxidative injury. However, strong vasoactive inhibition of NOS exacerbated the ischemia-reperfusion injury.     

Protective effects of high potassium administered after ischemic arrest against reperfusion injury in isolated rat hearts]

High potassium solution is one of the most commonly used cardioplegic solution, but the mechanism of action is still poorly defined. In the present study, isolated rat hearts were utilized to investigate the protective effects and mechanism of action of high potassium against ischemia/reperfusion injury. The results showed that high potassium (22 mmol/L) apparently improved the recovery of contraction amplitude (P < 0.01), inhibited the rise of resting tension (P < 0.01) and abolished ventricular fibrillation during reperfusion after global ischemia for 40 minutes. Moreover, high potassium could preserve myocardial Na+, K(+)-ATPase activity (P < 0.01) and inhibit sodium and calcium overload (P < 0.01) during reperfusion. The results indicate that small amount of high potassium solution (5 ml) administered even after ischemic arrest of rat heart has remarkable protective effects against ischemia/reperfusion injury at 37 degrees C. Its mechanism of action is at least partially by preserving Na+,K(+)-ATPase activity and inhibiting sodium and calcium overload.     

As2O3预处理对离体缺血再灌注心肌的保护作用及机制

目的研究三氧化二砷(As2O3)预处理抗心肌缺血再灌注损伤中热休克蛋白(HSP)27的作用及调控机制。方法将16只缺血再灌注心肌损伤大鼠随机分为观察组和对照组各8只,观察组再灌注前24 h腹腔注射As2O3预处理,对照组灌注生理盐水。观察两组再灌注后心功能指标、心肌超微结构及心肌组织HSP27表达变化。结果观察组左心室舒张末期压力(LVEDP)、左心室压力收缩速率(LV+dP/dtmax)、左心室压力舒张速率(LV-dP/dtmax)较对照组明显增高,超微结构损伤亦减轻,HSP27表达量明显增加(P均<0.01)。结论 As2O3预处理对缺血再灌注心肌损伤有保护作用;其机制可能为上调HSP27表达。