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1.
目的 探讨不同剂量硝酸甘油对大鼠血流动力学的影响及对大鼠离体缺血再灌注心肌的影响.方法 32只雄性SD大鼠随机分为4组(n=8):缺血再灌注(I/R)组、2μg· kg-1·min-1硝酸甘油预处理(PC1)组、4 μg·kg-1 ·min-1硝酸甘油预处理(PC2)组、6μg· kg-1·min-1硝酸甘油预处理(PC3)组.分别用静脉注射微量泵通过尾静脉持续1h泵入不同剂量的硝酸甘油,实时监测颈动脉血压及离体心功能,检测冠脉流量及心肌组织中cTnI及NO含量.结果 PC1组对大鼠血压无明显影响,但却明显改善心功能,增加冠脉流量,心肌组织中cTnI的含量较其他各组明显降低,NO含量较I/R组明显升高(P<0.05);PC3组血压及心功能明显降低,心肌组织中cTnI及NO含量极明显升高(P<0.05).结论 NO对缺血再灌注心肌的作用与剂量有关:静脉持续1h泵入小剂量硝酸甘油(2 μg·kg -1·min -1)对大鼠血流动力学无明显影响,但却能明显减轻心肌组织缺血再灌注损伤,大剂量硝酸甘油(6μg·kg-1·min -1)则加剧损伤. 相似文献
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目的:研究大剂量硝酸甘油(NG)对心肌缺血再灌注(MI/R)损伤的影响。方法:SD大鼠30只,制备离体MI/R模型,并将其随机分为2组:NG组和对照组。再灌注开始时NG组给予硝酸甘油(15μg/h,溶剂为950ml/L乙醇,加药速度50μl/h),对照组给予950ml/L乙醇(50μl/h),观察心功能指标,检测冠脉流出液中的肌酸激酶(CK)和乳酸脱氢酶(LDH)含量,用伊文氏兰-红四氮唑(TTC)染色和TUNAL法观测再灌注心肌坏死和凋亡程度。结果:大剂量NG抑制了再灌注后心功能的恢复,引起CK、LDH释放增加,促进心肌细胞坏死和凋亡。结论:大剂量NG加重了大鼠离体MI/R损伤。 相似文献
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目的:探讨乙醛脱氢酶2(ALDH2)激动剂(Alda-1)对硝酸甘油耐受(NT)大鼠心肌缺血/再灌注损伤(MI/RI)的影响。方法: 24只成年雄性SD大鼠随机分为4组:Con组、Alda-1组、NT组和NT+Alda-1治疗组,每组6只(n=6)。经静脉给予硝酸甘油10 mg/(kg·day)处理7 d,建立NT大鼠模型,治疗组在硝酸甘油给药的第5天起,同时输注Alda-110 mg/(kg·day) 3 d。模型建立后,采用冠脉左前降支结扎缺血30 min再灌注4 h建立在体大鼠急性心肌缺血/再灌注(MI/R)模型。术中监测血流动力学指标,再灌结束后检测血清乳酸脱氢酶(LDH)并取心肌组织检测心肌梗死面积、蛋白质羰基化程度和心肌内活性氧簇(ROS)的水平。结果: 离体血管灌流显示,硝酸甘油连续处理7 d,可导致大鼠血管内皮依赖性和内皮非依赖性舒张能力显著降低,提示出现NT。定量检测心肌ALDH2的活性发现Alda-1可显著改善NT导致的心肌ALDH2活性抑制。在NT情况下,MI/RI较对照组显著加重,表现为心肌收缩舒张速率显著降低,血清LDH的水平显著增加,心肌梗死面积扩大(均P<0.05)。与NT组相比,采用Alda-1治疗,可显著改善NT组大鼠的MI/RI(均P<0.05)。并且,Alda-1治疗可显著抑制NT情况下缺血/再灌注心肌中蛋白质羰基化程度和ROS的含量。结论: 激活ALDH2可显著抑制NT导致的MI/RI加重,其机制可能与减轻心肌蛋白质氧化损伤有关。 相似文献
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目的:观察乙醛脱氢酶2(ALDH2)激动剂Alda-1对Ⅰ型糖尿病(DM)小鼠心肌缺血/再灌注(I/R)损伤的影响,探讨羰基应激在DM心脏缺血性损伤易感性增高中的作用。方法:以C57BL/6雄性小鼠为实验对象,腹腔注射链脲佐菌素(STZ)制备Ⅰ型DM小鼠模型。将正常C57BL/6小鼠(20只)和DM小鼠(20只)随机分为I/R组和I/R+Alda-1治疗组,每组10只。采用冠状动脉左前降支结扎缺血30 min再灌注4 h建立在体小鼠急性心肌I/R模型,于再灌注前5 min经静脉以2 ml/(kg·h)速度分别输注生理盐水(NS)或Alda-1(16 mg/kg)并持续到再灌注结束。再灌注结束后取血检测血清乳酸脱氢酶(LDH)水平,取心肌组织检测ALDH2活性、心肌内活性氧簇(ROS)水平,蛋白羰基化程度和心肌梗死(MI)面积。结果:检测心肌ALDH2活性显示,DM小鼠心肌ALDH2活性较对照组显著降低。与对照组相比,DM小鼠心肌I/R损伤显著加重,表现为MI面积增大,血清LDH水平显著增加(均P0.05)。再灌注期Alda-1治疗可有效提高DM小鼠I/R心肌ALDH2活性(P0.05),并显著抑制DM小鼠的上述心肌I/R损伤(均P0.05)。DM组I/R心肌中蛋白质羰基化程度和ROS生成较对照组I/R心肌显著增加(均P0.05)。Alda-1治疗可有效改善DM小鼠I/R心肌中的蛋白质羰基化和ROS水平。结论:激活心肌ALDH2可显著改善DM小鼠心肌抗I/R损伤能力,其机制可能与减轻DM小鼠在I/R过程中导致的蛋白质氧化损伤有关。 相似文献
5.
目的研究肺缺血再灌注(ischemia/reperfusion。I/R)对乙醛脱氢酶2(ALDm)活性和含量,丙二醛(MethaneI)icarboxylicAldehyde,MDA)含量及4羟壬烯醛(4-hydroxy-2·noncnal,4-HNE)含量的影响。方法选取36只250—350g的雄性sD大鼠,采用在体原位肺I/R损伤模型,根据缺血再灌注时间不同随机分为A组(空白对照组即sham组)、B组(平衡灌注15rain组)、c组(缺血停呼吸30rain组)、D组(缺血停呼吸60min组)、E组(再灌注恢复呼吸30min组)和F组(再灌注恢复呼吸60min组),每组6只。在观察结束后取肺组织检测ALDH2活性和含量,MDA和4.HNE含量。结果A组、B组、C组、D组、E组和F组ALDH2活性分别为(2.26±0.45,2.30±0.48,2.40±0.69,2.21±0.42,2.21±0.42和2.16±0.62),含量分别为(0.91±0.11,1.21±0.61,1.23±0.38,1.11±0.38,1.00±0.47和O.92±0.34)组间差异无统计学意义。D组、E组和F组大鼠肺MDA含量(11.03±0.51,12.10±0.29和11.73±0.57)较A组和B组(10.35±0.52和10.30±0.56)升高,差异有统计学意义(P〈0.05);E组和F组大鼠肺MDA含量高于c组(10.87±0.62)和D组,差异有统计学意义(P〈0.05);其他各组之间差异无统计学意义。D组、E组和F组大鼠肺4-HNE含量(2.15±0.09,2.81±0.22和2.76±0.31)较A组和B组(1.93±0.1l和1.97±0.10)升高,差异有统计学意义(P〈0.05);E组和F组大鼠肺4-HNE含量高于c组(2.05±0.08)和D组,差异有统计学意义(P〈0.05);其他各组之间差异无统计学意义。结论随着缺血时间的延长,肺中醛类物质(MDA和4.HNE)开始蓄积,再灌注过程中醛类物质继续升高,ALDH2活性和含量未受到明显抑制 相似文献
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缺血期补充硝酸甘油对离体大鼠心脏心肌缺血再灌注损伤的作用 总被引:2,自引:0,他引:2
刘海波 Takayuki Tsuji Fumio Yamamoto Toshia Fujisato Hidekazu Hirai Fujio Miyawaki 《中国循环杂志》1999,14(4):0
目的:观察离体大鼠心脏缺血期补充一氧化氮(NO)供体对缺血再灌注损伤的影响。 方法:将26只离体大鼠心脏缺血30分,再灌注60分。分为两组,用药组(15只)及对照组(11 只)。用药组于缺血期给予4.4×10- 3 mm ol/L硝酸甘油(nitroglycerin,NTG,一种NO供体),碳酸氢盐缓冲液灌注。对照组仅给予碳酸氢盐缓冲液灌注。全部心脏均测定NO释放量、肌酸激酶漏出量及(或)心脏功能。 结果:用药组大鼠心脏,使用NTG表现为两种效应。其中部分大鼠心脏(非心室颤动组,n= 7),NTG增加肌酸激酶漏出量,减弱再灌注期心脏功能的恢复,伴随缺血期NO释放量的增加。对另一部分大鼠心脏(心室颤动组,n= 8),NTG减少肌酸激酶的释放,但心脏于再灌注期持续心室颤动,缺血期NO释放量无明显增加。 结论:缺血期给予同一剂量NTG对心肌缺血再灌注损伤产生双重效应,既可增加心肌损伤,又可减轻心肌损伤。 相似文献
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目的:探讨P2Y受体激动剂尿苷三磷酸(UTP)对于大鼠心脏缺血/再灌注损伤(I/RI)的延迟性拮抗作用。方法:24只SD大鼠随机分为4组:实验对照组、UTP组、UTP+苏拉明(suramin,SRM)组及SRM组。所有大鼠尾静脉给药24 h后,建立Langendorff离体心脏灌流模型。平衡10 min后全心停灌,25 min后复灌,持续再灌40 min。观察心脏再灌注前后血流动力学指标及心肌超微结构,记录心脏表面心电图计算心律失常的发生率,收集冠脉流出液,用全自动生化分析仪测量乳酸脱氢酶(LDH)的水平。结果:复灌后第5 min和25 min时,UTP组的左室发展压(LVDP)、左室压力微分(±dp/dtmax)恢复率均优于实验对照组(P0.05,P0.01);冠脉流出液中LDH的水平明显值降低(P0.01);复灌第5~15 min和第25~35min时的心律失常的发生频率均显著下降(P0.05,P0.01);心肌超微结构的损伤减轻。而以SRM与UTP同时作用后,UTP对心脏的保护作用则被取消。SRM组与实验对照组相比各项指标无明显变化。结论:UTP预处理可对心脏I/RI产生延迟性拮抗作用;而P2Y受体拮抗剂SRM可取消这种作用,表明UTP对心脏的保护作用是通过P2Y受体介导的。 相似文献
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10.
《中国老年学杂志》2014,(5)
目的研究缺血后处理对局灶性缺血和再灌注所造成脑损伤和神经炎症的影响。方法将成年雄性Wistar大鼠随进分为假手术组、局灶性缺血组、缺血后处理组。通过大脑中动脉闭塞术制备局灶性缺血,缺血后处理即在缺血后2 h进行3次30 s/30 s的再灌注/再阻塞。对脑梗死体积、神经系统功能、肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β的转录水平、TNF-α、IL-1β和TLR2的表达水平进行检查。结果缺血后处理组的脑梗死体积显著小于局灶性缺血组,神经系统功能也得到显著改善。此外,缺血后处理组抑制了TNF-α和IL-1β的转录,及TNF-α、IL-1β和TLR2的表达。结论缺血后处理组可以保护由局灶性缺血/再灌注造成的脑损伤并改善其神经系统功能,这与TNF-α和IL-1β转录的弱化,及TNF-α、IL-1β、TLR2表达的抑制有关。 相似文献
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Humanin exerts cardioprotection against cardiac ischemia/reperfusion injury through attenuation of mitochondrial dysfunction 下载免费PDF全文
Savitree Thummasorn Nattayaporn Apaijai Sasiwan Kerdphoo Krekwit Shinlapawittayatorn Siriporn C. Chattipakorn Nipon Chattipakorn 《Cardiovascular therapeutics》2016,34(6):404-414
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Arnau Panisello-Roselló Alexandre Lopez Emma Folch-Puy Teresa Carbonell Anabela Rolo Carlos Palmeira René Adam Marc Net Joan Roselló-Catafau 《World journal of gastroenterology : WJG》2018,24(27):2984-2994
Aldehyde dehydrogenase 2(ALDH2) is best known for its critical detoxifying role in liver alcohol metabolism. However, ALDH2 dysfunction is also involved in a wide range of human pathophysiological situations and is associated with complications such as cardiovascular diseases, diabetes mellitus, neurodegenerative diseases and aging. A growing body of research has shown that ALDH2 provides important protection against oxidative stress and the subsequent loading of toxic aldehydes such as 4-hydroxy-2-nonenal and adducts that occur in human diseases, including ischemia reperfusion injury(IRI). There is increasing evidence of its role in IRI pathophysiology in organs such as heart, brain, small intestine and kidney; however, surprisingly few studies have been carried out in the liver, where ALDH2 is found in abundance. This study reviews the role of ALDH2 in modulating the pathways involved in the pathophysiology of IRI associated with oxidative stress, autophagy and apoptosis. Special emphasis is placed on the role of ALDH2 in different organs, on therapeutic "preconditioning" strategies, and on the use of ALDH2 agonists such as Alda-1, which may become a useful therapeutic tool for preventing the deleterious effects of IRI in organ transplantation. 相似文献
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新型缺血再灌注模式诱导小鼠心肌细胞凋亡 总被引:7,自引:0,他引:7
目的 探讨联用垂体后叶素(以下简称Pit)及硝酸甘油(NG)造成缺血再灌注损伤,诱导小鼠心肌细胞凋亡的实验条件及有关机制.方法 以昆明种小鼠为实验对象,单纯经腹腔注入20μ/kg的Pit者为Pit组:30min后再注入10mg/kg的NG者为Pit和NG联用组,记录两组0,5,20,33,60min的心电图(以下简称ECG).80min取出小鼠心脏,用透射电镜及DNA琼脂糖胶电泳观察心肌凋亡的发生.结果 ECG表明在5min及33min前后,t波高度发生显著变化(P<0.05),电泳出现凋亡特征性梯带,电镜下可观察到染色体浓集、边聚等心肌细胞凋亡的特征性变化.结论Pit和NG联用能有效地诱导小鼠心肌凋亡,其机制可能与缺血再灌注损伤有关. 相似文献
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Differential effects of membrane and soluble Fas ligand on cardiomyocytes: role in ischemia/reperfusion injury 总被引:6,自引:0,他引:6
Date T Mochizuki S Belanger AJ Yamakawa M Luo Z Vincent KA Cheng SH Gregory RJ Jiang C 《Journal of molecular and cellular cardiology》2003,35(7):811-821
Cardiomyocyte apoptosis by Fas ligand (FasL)/Fas signaling is associated with various pathophysiological conditions, such as ischemia/reperfusion injury and congestive heart failure. In this study, we tested the hypothesis that shedding of membrane FasL is a mechanism for downregulating FasL/Fas signaling and both membrane and soluble FasL are involved in cardiomyocyte hypoxia/reoxygenation (H/R) injury. We also examined the relative importance of mitochondrial damage and direct cleavage of the executioner caspases by activated initiator caspase 8 in the propagation of FasL/Fas signaling activated by either recombinant membrane FasL or H/R. We demonstrated that in neonatal rat cardiomyocytes maintained under normal culture conditions, recombinant human soluble FasL increased caspase 3 activation by twofold but did not reduce cell viability. In contrast, infection with a recombinant adenoviral vector expressing the non-cleavable human FasL (Ad2/nchFasL) resulted in cardiomyocyte death that was attenuated by soluble FasL. H/R increased the mRNA levels of both FasL and Fas and activated caspases 8, 9 and 3, indicating the activation of FasL/Fas signaling. Z-IETD.fmk and Z-LEHD.fmk, selective inhibitors for caspases 8 and 9, respectively, abolished caspase 3 activation induced by Ad2/nchFasL or H/R. Z-IETD.fmk also significantly reduced Ad2/nchFasL- or H/R-induced cardiomyocyte death. H/R potentiated membrane FasL-induced cell death. These results suggest that shedding of membrane FasL downregulates FasL/Fas signaling in cardiomyocytes and both membrane and soluble FasL contribute to H/R injury. Activation of FasL/Fas signaling by either recombinant membrane FasL under normal culture conditions or H/R causes cardiomyocyte death mainly through the mitochondrial damage/caspase 9 activation pathway. 相似文献
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近年来促红细胞生成素(erythropoietin,EPO)的非造血生物作用逐渐引起关注。研究表明,EPO 可以减轻缺血缺氧时心肌细胞的损伤,减少心肌细胞的调亡,从而使其可能成为预防和治疗心肌缺血再灌注损伤的一条途径。 相似文献
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微小RNA(microRNA,miRNA)是一类在进化上高度保守的小分子非编码RNA,大约南19~25个核苷酸组成,具有转录后渊控蛋白质编码基因表达的功能, 相似文献
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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。 相似文献
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Yildiz F Coban S Terzi A Ates M Aksoy N Cakir H Ocak AR Bitiren M 《World journal of gastroenterology : WJG》2008,14(33):5204-5209
AIM: To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. METHODS: Thirty rats were divided into three groups as sham (Group 1), control (Group 2), and Nigella sativa (NS) treatment group (Group 3). All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS (0.2 mL/kg) intraperitoneally, before ischemia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrifi ced. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were determined. Total antioxidant capacity (TAC), catalase (CAT), total oxidative status (TOS), oxidative stress index (OSI) and my-eloperoxidase (MPO) in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. RESULTS: The levels of liver enzymes in group 3 weresignifi cantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were signifi cantly lower in group 3 than the group 2. Histological tissue damage was milder in the NS treatment group than that in the control group. CONCLUSION: Our results suggest that Nigella sativa treatment protects the rat liver against to hepatic ischemia-reperfusion injury. 相似文献
19.
目的:观察葡萄糖酸镁对离体大鼠心肌缺血/再灌注(I/R)损伤的保护作用及可能机制。方法:将48只大鼠等分为对照组、I/R组、葡萄糖酸镁组。实验1:每组取8只大鼠,对照组用改良的K-H液持续灌注110min;I/R组用改良的K-H液灌流20min后,停灌30min,再灌注60min;葡萄糖酸镁组在改良的K-H液中加入葡萄糖酸镁2.4mmol/L,余同I/R组。检测心肌灌流液中肌酸激酶(CK),乳酸脱氢酶(LDH)含量,心肌组织中总超氧化物歧化酶(T-SOD)、丙二醛(MDA)含量。实验2:每组8只大鼠,实验过程基本与实验1相同,仅将再灌注时间改为120min,检测心肌细胞凋亡指数(AI)。观察实验1、2合组再灌注心律失常发生情况。结果:葡萄糖酸镁组与I/R组相比,室性心律失常发生率显著下降(VT:43.8%对100.0%,VF:12.5%对75.0%,P<0.01);再灌流出液中CK、LDH含量显著降低[CK:(121.76±0.75)U/L对(132.33±1.73)U/L,LDH:(51.94±1.93)U/L对(62.73±2.18)U/L,P<0.01];心肌组织T-SOD活性显著升高[(49.12±0.54)NU/mg对(40.09±1.64)NU/mg,P<0.01];MDA含量、细胞凋亡指数显著降低[MDA:(3.05±0.19)μmol/g对(3.94±0.16)μmol/g,AI:(27.79±1.59)%对(33.61±2.10)%,P<0.01]。结论:葡萄糖酸镁对离体大鼠心肌I/R损伤具有保护作用,其机制可能与清除氧自由基、抗细胞凋亡有关。 相似文献