蛇床子素后处理对大鼠心肌急性缺血/再灌注损伤的保护作用

目的观察蛇床子素后处理对大鼠心肌急性缺血／再灌注损伤的作用。方法采用结扎左冠状动脉前降支制备在体大鼠急性心肌缺血／再灌注损伤模型。30只雄性Wistar大鼠随机分为伪手术（Sham）组、缺血／再灌注（I／R）组和缺血／再灌注＋蛇床子素后处理（Ost）组。采用BL-410生物信号记录分析系统记录大鼠左心室收缩压（LVSP）、左心室舒张末压（LVEDP）及左心室压力上升和下降最大速率（＋dp／dtmax）等心功能数据。实验结束后腹主动脉采血,采用ELISA方法检测血清肌酸激酶同工酶（CK—MB）、肌钙蛋白I（cTnI）含量,应用透视电镜对左室心尖部心肌组织超微结构进行形态学观察。结果与Sham组相比,I／R组大鼠心肌超微结构发生明显改变,心脏收缩、舒张功能显著降低,血清CK—MB及cTnI含量均显著增高。与I／R组比较,Ost组大鼠心肌超微结构损伤明显减轻,心功能明显改善,血清CK—MB及cTnI含量显著降低。结论蛇床子素后处理对急性心肌缺血／再灌注所致的大鼠心肌损伤具有保护作用。     

低灌注处理对家兔心肌缺血再灌注损伤的影响

目的观察低灌注处理对心肌缺血/再灌注(I/R)损伤家兔凋亡基因bcl-2、caspase 3表达及心功能的影响。方法家兔16只随机分为2组:心肌I/R组、低灌注处理组。记录两组家兔缺血前、缺血30 min及再灌180 min时的左室收缩峰压(LVSP)、左室舒张末压(LVEDP)和左室内压最大收缩/舒张变化速率(±dp/dtmax);运用免疫组化法检测心肌组织bcl-2蛋白表达;运用RT-PCR法检测心肌bcl-2、caspase-3 mRNA的表达。结果与对照组比较,低灌注处理组的±dp/dtmax、bcl-2 mRNA表达、bcl-2蛋白表达增高,而caspase-3 mRNA表达降低(P<0.05)。结论低灌注处理上调抑凋亡基因bcl-2、下调促凋亡基因caspase3的表达并能改善心肌I/R家兔的心功能。     

龙血竭总黄酮对新西兰兔心肌缺血/再灌注损伤作用的研究

目的研究龙血竭总黄酮对新西兰兔心肌缺血/再灌注损伤的保护作用。方法将30只新西兰兔随机分为三组,每组10只。采用结扎新西兰兔左冠状动脉前降支法,建立心肌缺血/再灌注损伤模型。观察心肌组织HE染色的结构变化,测量左心室内压最大上升速率(+dp/dtmax),检测心肌肌酸激酶同工酶(CK-MB)。结果龙血竭处理组心肌组织结构明显好于缺血/再灌注组;缺血/再灌注组和龙血竭处理组+dp/dtmax均明显低于假手术组(P0.01),龙血竭处理组+dp/dtmax高于缺血/再灌注组(P0.01);缺血/再灌注组CK-MB水平明显高于假手术组(P0.01),龙血竭处理组CK-MB水平高于假手术组(P0.05),并低于缺血/再灌注组(P0.01)。结论龙血竭总黄酮能够改善心肌缺血/再灌注损伤,保护心肌组织结构,稳定细胞膜结构,减少心肌CK-MB漏出,提高缺血/再灌注损伤模型心肌的收缩功能。     

芍药苷预处理对大鼠离体缺血再灌注损伤心脏的保护作用

目的 观察芍药苷预处理对大鼠离体缺血再灌注损伤心脏的保护作用,探讨其可能机制.方法 建立Langendorff离体心脏灌注模型.随机将SD雄性大鼠分为6组,即空白对照(Con)组、单纯缺血再灌注(I/R)组、缺血预处理(IPC)组、不同浓度(15 mg/L,30 mg/L,60 mg/L)芍药苷预处理组(PF1PF3组).Chart5软件分析缺血前,再灌注后20 min、40 min心功能参数,包括:左心室收缩压(LVSP)、左心室内压变化最大速率(dp/dtmax)、心率(HR)、冠脉流出量(CF);收集灌注末心脏标本,制备心肌匀浆,检测超氧化物歧化酶(SOD)、丙二醛(MDA)、乳酸脱氢酶(LDH)、肌酸激酶(CK)值;电镜观察再灌注末心肌细胞超微结构并拍照.结果 IPC、PF预处理组在心功能恢复及心肌酶指标活力方面均优于I/R组(P<0.01);心肌超微结构损伤减轻.结论 芍药苷预处理对大鼠离体心脏能产生保护作用.     

黄芪预处理大鼠心肌保护效应的实验研究

目的本文研究黄芪预处理对大鼠心肌的保护效应以及心肌保护效应与热休克蛋白之间的关系.方法用在体大鼠复制缺血再灌注损伤模型,将大鼠随机分成对照组、缺血再灌组、黄芪组三组,观察心肌组织学、SOD酶的活性、MDA含量变化、心肌梗死范围和HSP70蛋白的表达的变化.结果黄芪预处理组明显减少梗死面积和减少MDA的产生,保护细胞中SOD酶活性和超微结构,HSP70表达水平明显高于对照组及缺血再灌注组.结论黄芪处理可减少缺血再灌注心肌损伤,并能诱导心肌细胞HSP70的表达.     

不同浓度硝酸甘油对心脏缺血/再灌注的作用及ALDH2的作用

目的 探讨不同浓度硝酸甘油(GTN)对离体大鼠心脏缺血/再灌注损伤的作用,进一步分析线粒体乙醛脱氢酶2(ALDH2)在其中的作用.方法 采用离体大鼠心脏Langendorff灌流方法,局部结扎冠状动脉左前降支30 min,复灌30 min复制缺血/再灌注模型.实验分五组,正常对照组,单纯缺血/再灌注组,GTN低浓度组(10 -8 mol/L GTN),中浓度组(10-7 mol/L GTN)及高浓度组(2×10 -6 mol/L GTN).测定心室动力学指标和复灌期间冠脉流出液中乳酸脱氢酶( lactate dehydrogenase,LDH)含量,RT-PCR测定左心室前壁心尖组织线粒体ALDH2基因mRNA表达水平.结果 与单纯缺血/再灌注组相比,GTN低浓度组左心室发展压(LVDP)、室内压最大上升/下降速率(±dp/dtmax)均增高,左心室舒张末压(LVEDP)降低,中浓度组无明显差异,高浓度组LVDP和±dp/dtmax均降低;LVEDP增高.与缺血/再灌注组相比,正常对照组和低浓度GTN组心肌组织ALDH2 mRNA表达增高,中浓度无明显差异,高浓度组大鼠心肌ALDH2 mRNA表达降低.结论 低浓度GTN可对抗心肌缺血/再灌注损伤,高浓度GTN加重损伤,中浓度GTN对损伤影响不大,此现象可能与不同浓度GTN引起心肌ALDH2的释放量不同有关.     

缺血预处理前加用益母草碱对大鼠心肌再灌注损伤的影响

目的：观察缺血预处理前加用益母草碱（Leonurine）对大鼠心肌再灌注损伤的影响并探讨其作用机制.方法：将SD大鼠随机分为4组,建立大鼠离体心脏左心作功模型,缺血期间均间断灌注心脏停搏液.结果：再灌注期,缺血预处理前加用益母草碱组心脏的左室收缩压（LVSP）、左室舒张末压（LVEDP）、左室内压上升最大速率（＋dp/dtmax）和左室内压下降最大速率（-dp/dtmax）恢复最佳,心肌组织丙二醛（malondialdehyde,MDA）含量低、超氧化物歧化酶（superoxide dismutase,SOD）活性高,能明显减轻心肌组织超微结构的损伤.结论：缺血预处理前加用益母草碱能强化缺血预处理对大鼠心肌再灌注的保护作用.     

黄芪预处理大鼠心肌保护效应的实验研究

目的 本文研究黄芪预处理对大鼠心肌的保护效应以及心肌保护效应与热休克蛋白之间的关系。方法 用在体大鼠复制缺血再灌注损伤模型,将大鼠随机分成对照组、缺血再灌组、黄芪组三组、观察心肌组织学、SOD酶的活性、MDA含量变化、心肌梗死范围和HSP70蛋白的表达的变化。结果 黄芪预处理组明显减少梗死面积和减少MDA的产生,保护细胞中SOD酶活性和超微结构,HSP70表达水平明显高于对照组及缺血再灌注组。结论 黄芪处理可减少缺血再灌注心肌损伤,并能诱导心肌细胞HSP70的表达。     

Notch3介导RhoA/ROCK/Hif1α轴对心肌梗死心功能的影响

目的 分析Notch3介导RhoA/ROCK/Hif1α轴对心肌梗死(MI)心功能的影响。方法 将45只雄性SD大鼠随机分为假手术组、模型组和Notch3过表达组三组,每组各15只。大鼠心肌注射Notch3慢病毒过表达后构建MI模型。术后12周检测心功能及心脏血流动力学指标,观察心肌组织结构,并检测心肌组织Notch3和RhoA/ROCK/Hif1α轴相关蛋白水平。结果 与假手术组比较,模型组大鼠心肌组织Notch3表达水平、左心室射血分数(LVEF)、左心室舒张末压(LVEDP)显著降低,左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左心室收缩末压(LVESP)、左心室压力最大上升速率(LV+dp/dtmax)、左心室压力最大下降速率(LV-dp/dtmax)、心肌组织RhoA、ROCK1、ROCK2、Hif1α表达水平显著增加(P<0.05);Notch3过表达组大鼠LVESD和LVEDD显著小于模型组,心肌组织Notch3表达水平、LVEF、LVEDP显著高于模型组(P<0.05);LVESP、LV+dp/dtmax和LV-dp/dtmax、心肌...     

吗啡对大鼠离体心脏再灌注损伤的保护作用

目的研究吗啡对大鼠离体心脏缺血再灌注损伤的保护作用及其机制。方法32只雄性wistar大鼠随机分为对照组,吗啡组,吗啡+纳络酮组,吗啡+格列本脲组,建立离体工作心脏模型。4℃St.ThomasⅡ停搏液诱导心脏停搏30min,观察缺血再灌注后吗啡对心排血量(CO)、左心室压力微分(±dp/dtmax)、左心室舒张压(LVDP)恢复率及乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、心肌超微结构的影响,并观察纳络酮和格列本脲对吗啡作用的影响。结果吗啡组CO、±dp/dtmax、LVDP的恢复率优于其他各组(P<0.05),LDH漏出明显低于其他组(P<0.05),心肌线粒体等超微结构损伤明显减轻;纳络酮和格列本脲可以完全阻断吗啡的心肌保护作用。结论吗啡可以减轻大鼠心肌的缺血再灌注损伤。吗啡是通过心脏局部的阿片受体及心肌细胞三磷腺苷(ATP)敏感性钾通道(KATP通道)介导产生心肌保护作用。     

The temporal relationship between p38 MAPK and HSP27 activation in ischaemic and pharmacological preconditioning

An ischaemic preconditioning protocol and subsequent sustained ischaemia were characterized by activation and attenuation of p38 MAPK phosphorylation, respectively. However, the significance of events downstream of p38 MAPK needs investigation. Therefore the temporal relationship between phosphorylation of p38 MAPK and its downstream substrate HSP27 was studied during either an ischaemic or –adrenergic preconditioning protocol and during sustained ischaemia.Isolated rat hearts were preconditioned (with or without a p38 MAPK inhibitor, SB203580) with 1 × 5 min or 3 × 5 min global ischaemia or 5 min –adrenergic stimulation (10^–7 M isoproterenol), followed by 25 min sustained ischaemia and 30 min reperfusion. Hearts were freeze–clamped at different time intervals and fractionated to determine p38 MAPK and HSP27 phosphorylation, via Western blotting.Significant phosphorylation of cytosolic p38 MAPK and membrane (myo–fibrillar) HSP27 occurred at the end of the first preconditioning episode. However, p38 MAPK phosphorylation disappeared during subsequent preconditioning episodes, while HSP27 phosphorylation was maintained for the duration of the protocol. Similar changes in p38 MAPK and HSP27 occurred with 5 min –adrenergic preconditioning. After 25 min ischaemia, significant phosphorylation of cytosolic and membrane HSP27 was observed, while p38 MAPK phosphorylation was attenuated in ischaemic and –adrenergic preconditioned compared to non–preconditioned hearts. SB203580–induced abolishment of p38 MAPK and HSP27 phosphorylation during the triggering phase of both preconditioning protocols reversed the changes in these parameters seen after sustained ischaemia.The results suggest that p38 MAPK activation triggers HSP27 phosphorylation during both the preconditioning protocols and during sustained ischaemia. Protection of preconditioned hearts during sustained ischaemia was characterized by phosphorylation of both cytosolic and myofibrillar HSP27.     

AMPK抑制剂P5499拮抗无钙预处理心肌保护作用

目的:观察腺苷酸活化的蛋白激酶(AMPK)抑制剂P5499对短暂无钙预处理心肌保护作用的影响。方法:对健康SD雄性大鼠心脏行Langendorff离体灌流,实验全程记录心脏冠脉流量(CF)、左心室内压(LVP)、左室舒张末压(LVEDP)、室内压最大变化速率(±dp/dtmax)及心率(HR),并计算左室发展压(LVDP)和心率-压力乘积(RPP)评价心功能的变化。再灌注结束后,采用2、3、5-氯化三苯基四氮唑(TTC)染色法评价心肌梗死(MI)面积的变化。结果:缺血/再灌注(I/R)后,心功能显著降低,CF明显减少(P<0.01),MI面积的比率为(39.6±1.49)%。短暂无钙预处理(CPC)可使LVEDP明显降低(P<0.05),CF、LVDP、±dp/dtmax及RPP均明显改善(P<0.01),MI面积显著缩小(P<0.01)。缺血前单独给予P5499对心功能、CF及MI面积无明显影响,但其可显著逆转CPC的心肌保护作用(P<0.01)。结论:AMPK可能是Ca2+预处理产生心肌保护信号的下游分子。     

Protein kinase C-dependent activation of P44／42 mitogen-activated protein kinase and heat shock protein 70 in signal transduction during hepatocyte ischemic preconditioning

AIM: To investigate the significance of protein kinase C (PKC), P44/42 mitogen-activated protein kinase (MAPKs) and heat shock protein (HSP)70 signal transduction during hepatocyte ischemic preconditioning. METHODS: In this study we used an in vitro ischemic preconditioning (IP) model for hepatocytes and an in vivo model for rat liver to investigate the significance of protein kinase C (PKC), P44/42 mitogen-activated protein kinase (P44/42 MAPKs) and heat shock protein 70 (HSP70) signal transduction in IP. Through a normal liver cell hypoxic preconditioning (HP) model in which cultured normal liver cells were subjected to 3 cycles of 5 rain of incubation under hypoxic conditions followed by 5 rain of reoxygenation and subsequently exposed to hypoxia and reoxygenation for 6 h and 9 h respectively. PKC inhibitor, activator and MEK inhibitor were utilized to analyze the phosphorylation of PKC, the expression of P44/42 MAPKs and HSP70. Viability and cellular ultrastructure were also observed. By using rat liver as an in vivo model of liver preconditioning (3 cycles of 10-min occlusion and 10-min reperfusion), in vivo phosphorylation of PKC and P44/42MAPKs, HSP70 expression were further analyzed. AST/ALT concentration, cellular structure and ultrastruture were also observed. All the data were statistically analyzed. RESULTS: Similar results were obtained in both in vivo and in vitro IP models. Compared with the control withouts IP (or HP), the phosphorylation of PKC and P44/42 MAPKs and the expression of HSP70 were obviously increased in IP (or HP) treated model in which cytoprotection could be found. The effects of preconditioning were mimicked by stimulating PKC with 4β phorobol-12-myristate 13-acetate (PMA). Conversely, inhibiting PKC with chelerythrine abolished the protection given by preconditioning. PD98059, inhibitor of MEK (the upstream kinase of P44/42MAPKs), also reverted the cytoprotection exerted by preconditioning. CONCLUSION: The results demonstrate that preconditioning induces a rapid activation of P44/421VlAPKs and PKC activation plays a pivotal role in the activation of P44/42 MAPKs pathway that participates in the preservation of liver cells. HSP expression is regulated by signals in PKC dependent P44/42 MAPKs pathway.     

去甲肾上腺素预处理对大鼠供心热休克蛋白70、一氧化氮及一氧化氮合酶表达的影响

目的:探讨去甲肾上腺素预处理是否可诱导心肌热休克蛋白70(HSP70)的合成,并研究其对供心一氧化氮(NO)、一氧化氮合酶(NOS)的影响,探讨去甲肾上腺素预处理心肌保护作用机制。方法:Wistar大鼠18只,分为2组:对照组(C,n=9),腹腔注射0.9%氧化钠注射液0.5 mL,24 h后取离体心脏灌注(Histidine-tryptophan-ketoglutarte,HTK)心脏保护液,4℃保存3 h后建立Langendorff离体心脏灌注模型,灌注(Krebs-Henseleit,K-H)液2 h;实验组(E,n=9)腹腔注射重酒石酸去甲肾上腺素(溶于0.9%氯化钠液中)3.1μmol/kg(0.53 mg/kg),腹腔注射24 h后取离体心脏,处理方法同C组。测定心肌HSP70、NO、NOS的含量以及相关生化指标并做统计学处理比较。结果:HSP70含量E组较C组明显增高(P<0.01),NO、NOS的含量E组较C组明显增多(P<0.01),生化指标E组明显优于C组。结论:去甲肾上腺素预处理能诱导供心心肌组织HSP70、NO、NOS高表达,其对供心具有明显的保护效应,并且其促进心肌NO、NOS的表达,这可能是去甲肾上腺素预处理发挥供心保护作用的机制之一。     

超速起搏预适应的延迟保护与热休克蛋白27的表达

目的：观察超速心室起搏（VOP）预适应延迟保护阶段热休克蛋白27（HSP27）的表达水平。方法：新西兰兔24只,随机分为3组,缺血再灌注（I/R）空白对照组,起搏组,起搏＋放线菌素D组。制作I/R和超速起搏预适应的动物模型,检测肌酸激酶（CK）和肌酸激酶-同工酶（CK-MB）水平的变化,动态描记再灌注时心电图,以免疫组织化染色法检测HSP27抗原表达水平。结果：I/R后起搏组心肌酶的水平均明显低于I/R空白对照组和起搏＋放线菌素D组（P〈0.01）;I/R空白对照组在再灌注过程中共有5只（62.5%）发生心律失常,起搏＋放线菌素D组有4只（50.0%）,而起搏组无心律失常发生。起搏组心律失常发生率明显低于I/R空白对照组和起搏＋放线菌素D组（P〈0.05）。起搏组HSP27阳性表达＋＋者（37.5%）明显高于I/R空白对照组和起搏＋放线菌素D组（0,12.5%,P〈0.05）。结论：心室超速起搏预适应有心脏保护作用,其机制可能与热休克蛋白27表达增加密切相关。     

甘氨酸对大鼠肝移植缺血再灌注损伤库普弗细胞CD14和核因子-κB的影响

目的 探讨甘氨酸对大鼠肝移植缺血再灌注损伤库普弗细胞CD14和核因子-κB(NF-κB)的影响。 方法 将大鼠分为肝移植缺血再灌注组、等渗盐水预处理组、甘氨酸预处理组,检测再灌注后受体存活率、肝脏功能和病理组织学改变。分离培养再灌注后库普弗细胞,检测细胞CD14 mRNA的表达、NF-κB活性、培养上清液肿瘤坏死因子α和白细胞介素-1分泌情况。 结果 甘氨酸预处理能明显提高大鼠术后1周存活率(x2值分别为6.67和8.57,P值均<0.0 1)、改善肝功能、减轻肝脏病理组织学改变;甘氨酸预处理能明显下调库普弗细胞CD14 mRNA的表达(F=7.64,P<0.01)、降低NF-κB活性(F=11.47,P<0.01)、减少上清液肿瘤坏死因子α和白细胞介素-1分泌(F值分别为14.08和9.56,P值均<0.01)。 结论 甘氨酸能够有效地减轻肝移植后缺血再灌注损伤,其机制可能与抑制库普弗细胞CD14表达和NF-κB活性、减少肿瘤坏死因子α和白细胞介素-1的分泌有关。     

地塞米松对大鼠心肌缺血再灌注后细胞凋亡及金属硫蛋白表达的影响

目的观察地塞米松预处理对大鼠心肌缺血再灌注损伤的影响并探讨其作用机制。方法32只SD大鼠随机分成地塞米松组(16只)和对照组(16只),分别给予地塞米松(0.8mg/kg)和蒸馏水腹腔注射。预处理24h后,构建体外心脏缺血再灌注动物模型,动态观测缺血前期及再灌注期左心室发展压(LVDP)、左心室压力最大上升和下降速率(±dp/dtmax)、冠状动脉流出量(CF);测定冠状动脉流出液肌酸激酶同工酶(CK-MB)的漏出率;TUNEL法检测心肌细胞凋亡;Westernblot法检测金属硫蛋白(MT)、Bcl-2及Bcl-xl蛋白的表达;免疫组织化学法测定半胱天冬酶-3(caspase-3)的水平。结果与对照组比较,地塞米松组大鼠再灌注期LVDP、±dp/dtmax及CF得到改善(P<0.05);CK-MB的漏出率明显降低[(8.69±4.16)U/gvs(18.15±5.59)U/g,P<0.01];心肌细胞凋亡指数(10.18±1.99)%vs(14.66±2.97)%和caspase-3水平明显减少[(18.66±5.15)%vs(27.93±6.23)%,P<0.01],Bcl-xl(4.74±0.66)vs(1.69±0.73)和MT的表达明显增加[(3.09±1.07)vs(1.03±0.02),P<0.05],Bcl-2无明显变化(P>0.05)。结论地塞米松预处理对大鼠缺血再灌注的心肌具有保护作用,上调MT表达及抑制细胞凋亡可能是其机制之一。     

Impaired p38 MAPK/HSP27 signaling underlies aging-related failure in opioid-mediated cardioprotection

Cardioprotection and preconditioning mediated via G-protein-coupled receptors may be lost or impaired with advancing age, limiting ischemic tolerance and the ability to pharmacologically protect older hearts from ischemic injury. Our preliminary findings indicated a loss of delta-opioid receptor-mediated protection in aged vs. young mouse hearts, which may involve alterations in protective kinase signaling. In the present study, we tested the hypothesis that aging-related loss of opioid-triggered cardioprotection involves failure to activate p38 MAPK and its distal signaling targets. Langendorff-perfused hearts from young (10-14 weeks) or aged (24-26 months) C57 mice underwent 25-min ischemia and 45-min reperfusion in the presence or absence of 1 micromol/l DPDPE (delta-opioid agonist) or 1 micromol/l anisomycin (activator of p38 MAPK), and functional recovery and protein activation/phosphorylation were assessed. Contractile recovery was similar in untreated young and aged hearts (50+/-2% and 53+/-5%, respectively), and was enhanced by DPDPE in young hearts only (67+/-3%). Immunoblot analysis revealed that DPDPE comparably activated or phosphorylated GRK2, Akt, ERK1/2 and p70S6 kinase in young and aged hearts, whereas aging abrogated the stimulatory effects of DPDPE on p38 MAPK and HSP27. Treatment with anisomycin elicited comparable activation of p38 MAPK and HSP27 in both young and aged hearts, coupled with a pronounced and equivalent cardioprotection in the two groups (73+/-3% and 77+/-2%, respectively), an effect abolished by the p38 MAPK inhibitor, SB203580. These data indicate that aging-related loss of delta-opioid-mediated cardioprotection involves failure to activate p38 MAPK and HSP27. Direct targeting of this pathway elicits comparable protection in both age groups.     

Ecto-5'-nucleotidase plays a role in the cardioprotective effects of heat shock protein 72 in ischemia-reperfusion injury in rat hearts

OBJECTIVE: Heat shock protein 72 (HSP72) is involved in the myocardial self-preservation system under several conditions such as ischemia-reperfusion injury or late preconditioning. However, its mechanism is not fully understood. Ecto-5'-nucleotidase is a key enzyme for synthesizing adenosine and plays an important role in ischemic preconditioning. In this study, we tested the hypothesis that ecto-5'-nucleotidase plays a role in the cardioprotection of HSP72. METHODS: Rat hearts (H group, n=6) were transfected with HSP72 gene by an intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome complex. Control hearts (C group, n=6) were transfected with the beta-galactosidase gene. Following 30 min of normothermic ischemia, grafts were reperfused using Langendorff apparatus. RESULTS: The activity of ecto-5'-nucleotidase was significantly higher in H group than C group both before and after ischemia-reperfusion (H vs. C; 0.51+/-0.05 vs. 0.29+/-0.06, and 1.41+/-0.15 vs. 0.85+/-0.11 nmol/mg protein/min, P<0.05). H group also showed significant better functional recoveries than C group (P<0.05), as well as less creatine phosphokinase leakage (4.4+/-2.8 vs. 14.2+/-3.4 mU/min, P<0.05) and higher adenosine release (247.5+/-35.1 vs. 54.3+/-1.7 pmol/min, P<0.05). Administration of alpha,beta-methylene adenosine diphosphate (AMP-CP), an inhibitor of ecto-5'-nucleotidase, significantly diminished the tolerance to ischemia-reperfusion injury in H group (P<0.05). CONCLUSION: These results demonstrated that ecto-5'-nucleotidase activated by an overexpression of HSP72 attenuated ischemia-reperfusion injury in the rat myocardium. They suggest that ecto-5'-nucleotidase plays a role in the cardioprotective effects of HSP72 in rat hearts.     

负荷剂量氟伐他汀对心肌缺血再灌注损伤的保护作用——模拟缺血预适应

目的观察负荷剂量氟伐他汀预处理对在体大鼠心肌缺血再灌注损伤的保护作用。方法 84只大鼠随机分为12组,每组7只。其中氟伐他汀组（F-1~F-8组）分别于冠状动脉缺血前1、2、4、6、12、24、48和72 h灌胃氟伐他汀80 mg/kg;假手术组（Sham组）、缺血再灌注组（I/R组）、缺血预适应第一窗口组（IPC-1组）及第二窗口组（IPC-2组）灌胃等量生理盐水。建立大鼠心肌缺血再灌注损伤模型、缺血预适应保护模型及延迟保护模型。记录大鼠心律失常及心肌缺血、心肌梗死情况,测定血清乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）活性,光学显微镜及透射电镜下观察受损心肌细胞形态。结果氟伐他汀预处理组中,除F-5、F-6组外,其他组心肌梗死面积均较I/R组减小（P〈0.05）;负荷剂量氟伐他汀的保护作用呈现两个窗口,F-3、F-7组分别为其保护作用的最佳组（与I/R组比较,P〈0.05）;与IPC-1组比较,F-3组心肌缺血、心肌梗死程度、血清LDH和CK-MB均显著增高（P〈0.05）,心律失常评分差异无统计学意义（P〉0.05）。与IPC-2组比较,F-7组梗死面积有减少趋势（P〉0.05）,心肌梗死质量显著降低（P〈0.05）,缺血程度显著增高（P〈0.05）。结论负荷量氟伐他汀预处理对在体大鼠心肌缺血再灌注损伤的保护作用存在两个窗口,第一窗口较缺血预适应弱,第二窗口在减轻心肌梗死程度上有强于缺血预适应的趋势。