Effects of electroacupuncture of acupoints of the neiguan and ximen on ischemic myocardium energy metabolism with acute myocardial ischemia rats

Objective:To observe the effect of Electroacupuncture of Acupoints of the Neiguan(PC6)and Ximen(PC4)on its myocardial energy metabolism with acute myocardial ischemia rats caused by coronary artery ligation.Methods:Forty standard Spargue-Dawely(SD)rats were divided into four groups randomly,namely,group of Neiguan,group of Ximen,model group,sham group.The group of rats of myocardial ischemia were induced by coronary ligation,and the model rat of acute myocardial ischemia was prepared.The sham group had no ligation of the needle.After anesthesia was awakened,acupuncture was applied bilateral at Neiguan and Ximen of the group of Neiguan and Ximen,once a day at a fixed time for 14 days.The rats of model group and the sham group were not given acupunctured,but use the samely methods of Neiguan and Ximen groups to grap the rats at the same time everyday.After 14 days the experiment was over,observed the pathological changes of myocardial tissue by HE staining,detected the levels of free fatty acid(FFA),adenosine triphosphate(ATP)content,and the activities of Na^(+)-K^(+)-ATPase according to the reagents´demand.Results:Pathological results showed that acupuncuted at Neiguan and Ximen could improve the ischemic cardiomyocyte injury.Compared with the sham group,the levels of FFA in model group were increased(p<0.01),the levels of ATP,the activities of Na^(+)-K^(+)-ATPase were all decreased(p<0.01);Compared with the model group,the levels of FFA were decreased(p<0.05,p<0.01),the levels of ATP,the activities of Na^(+)-K^(+)-ATPase were improved.Conclusion:Acupuncturing at the Pericardium Meridian can alleviate the cell injury by myocardial ischemia,and also can improve the myocardial energetic metabolism in acute myocardial ischemia.

Impaired tricarboxylic acid cycle flux and mitochondrial aerobic respiration during isoproterenol induced myocardial ischemia is rescued by bilobalide

There is an urgent need to elucidate the pathogenesis of myocardial ischemia(MI)and potential drug treatments.Here,the anti-MI mechanism and material basis of Ginkgo biloba L.extract(GBE)were studied from the perspective of energy metabolism flux regulation.Metabolic flux analysis(MFA)was performed to investigate energy metabolism flux disorder and the regulatory nodes of GBE components in isoproterenol(ISO)-induced ischemia-like cardiomyocytes.It showed that[U-13 C]glucose derived m+2 isotopologues from the upstream tricarboxylic acid(TCA)cycle metabolites were markedly accumulated in ISO-injured cardiomyocytes,but the opposite was seen for the downstream metabolites,while their total cellular concentrations were increased.This indicates a blockage of carbon flow from glycolysis and enhanced anaplerosis from other carbon sources.A Seahorse test was used to screen for GBE components with regulatory effects on mitochondrial aerobic respiratory dysfunction.It showed that bilobalide protected against impaired mitochondrial aerobic respiration.MFA also showed that bilobalide significantly modulated the TCA cycle flux,reduced abnormal metabolite accumulation,and balanced the demand of different carbon sources.Western blotting and PCR analysis showed that bilobalide decreased the enhanced expression of key metabolic enzymes in injured cells.Bilobalide’s efficacy was verified by in vivo experiments in rats.This is the first report to show that bilobalide,the active ingredient of GBE,protects against MI by rescuing impaired TCA cycle flux.This provides a new mechanism and potential drug treatment for MI.It also shows the potential of MFA/Seahorse combination as a powerful strategy for pharmacological research on herbal medicine.

CHANGES IN NEUROPEPTIDES AFTER MUSIC EXPOSURE 429Cardioprotective effect of ivabradine via the AMPK/SIRT1/PGC-1αsignaling pathway in myocardial ischemia/reperfusion injuryinduced in H9c2 cell

Post-resuscitation myocardial dysfunction(PRMD)is the most severe myocardial ischemia-reperfusion injury(MIRI)and is characterized by difficult treatment and poor prognosis.Research has shown the protective effects of the rational use of ivabradine(IVA)against PRMD,however,the molecular mechanisms of IVA remain unknown.In this study,an ischemia-reperfusion injury(IRI)model was established using hypoxic chambers.The results demonstrated that pretreatment with IVA reduced IRI-induced cytotoxicity and apoptosis.IVA attenuated mitochondrial damage,eliminated excess reactive oxygen species(ROS),suppressed IRI-induced ATP and NAD+,and increased the AMP/ATP ratio.We further found that IVA increased the mRNA levels of sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α)and upregulated the expression levels of phosphorylated AMP-activated protein kinase(p-AMPK)/AMPK,SIRT1,and PGC-1αproteins.Interestingly,no change in AMPK mRNA levels was observed.Cardiomyocyte energy metabolism significantly changed after IRI.The aim of this study was to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1αsignaling pathway in myocardial ischemia/reperfusion injury-induced in H9c2 cell.

Effect of Yiqi Huoxue Decoction on the metabolomics of acute myocardial infarction rats

Objective:To explore the effect of Yiqi Huoxue Decoction on the metabolomics of acute myocardial infarction rats.Method:Left anterior descending coronary artery ligation was used to establish an acute myocardial infarction animal model.The rats were randomly divided into model,perindopril,QishenYiqi Dropping Pill and Yiqi Huoxue Decoction groups and compared with a shamoperation group.Blood metabolite changes were detected by nuclear magnetic resonance metabolomics 7 and 28 days after operation.Metabolite differences between the administration and model groups were analyzed.P-values of the differences in metabolite levels between the drug and model groups were statistically analyzed.Results:Compared with the sham-operation group,there were 22 altered metabolites in the model group identified after 7 days and 15 identified after 28 days.Products of energy,carbohydrate,lipid and amino acid metabolism were the primary metabolites observed in the analyzed samples.Conclusion:After intervention with traditional Chinese medicine,there were clear changes in energy,carbohydrate,lipid and amino acid metabolism that restored the metabolic phenotype to the normal range,thus repairing the damage caused by myocardial infarction.

Effects of Corocalm (Shuguan Capsule,疏冠胶囊) on Acute Myocardial Ischemia in Anesthetized Dogs

Objective： To investigate the effects of Corocalm （Shuguan Capsule, 疏冠胶囊） on acute myocardial ischemia in anesthetized dogs and its possible therapeutic mechanism. Methods： The acute ischemia model was established by ligating the left anterior descending （LAD） artery. Twenty- five dogs were randomly divided into 5 groups （5 dogs in each group）： the control group （treated with normal saline 3 mL/kg）, the refined Guanxin Capsule group （精制冠心胶囊, GXC 200 mg/kg）, high and low dose Corocalm groups （48.5 mg/kg for low dose group and 194.0 mg/kg for high dose group） and the Diltiazem group （5 mg/kg）. The animals were treated via a single duodenal administration after the model was established. The experiments used epicardial electrocardiogram （EECG） to measure the scope and degree of myocardial ischemia. Simultaneously, the coronary blood flow （CBF） and serum activity levels of creatine phosphokinase （CK） and lactate dehydrogenase （LDH） were measured by electromagnetic flow meter and automatic biochemical analyzer respectively. The plasma endothelin （ET） content was quantified by radioimmunoassay. Results： Corocalm （48.5 mg/kg and 194.0 mg/kg） significantly decreased the degree and scope of myocardial ischemia, reduced the infarct area, markedly increased the CBF, and inhibited the increase of CK and LDH activities and ET levels induced by myocardial ischemia/infarction. Conclusion： Corocalm could improve the state of acute myocardial ischemia and infarction in dogs. The mechanism of action might be correlated to increasing CBF, inhibiting CK and LDH activities and preventing ET release.

铁死亡用于心肌缺血再灌注损伤治疗的研究进展

铁死亡是一种铁依赖性的脂质过氧化介导细胞膜损伤致细胞死亡的新方式,其受多种细胞代谢途径的调控,包括铁代谢、脂质代谢、氧化还原系统等,许多器官的损伤和退行性病变均与其相关,在治疗缺血性疾病和脂质过氧化相关的退行性变疾病中有巨大潜力。心肌缺血再灌注损伤(MIRI)是急性心肌梗死患者进行血运重建治疗后最常见的死亡原因,近年的研究表明铁死亡与MIRI密切相关,通过氧化应激、铁代谢、脂质代谢、内质网应激、炎症反应等影响MIRI,干预再灌注过程中的铁死亡可以有效改善心功能,减少梗死面积。本文就铁死亡在MIRI中的具体作用及相关研究进展予以综述。

槲皮素对心肌缺血后线粒体能量代谢功能的影响

目的探究槲皮素对心肌缺血后线粒体能量代谢功能的影响。方法将H9c2心肌细胞分为空白组,模型组,槲皮素高、中、低剂量组(40、20、10μmol/L)和阳性对照组(环孢菌素A 1μmol/L),细胞缺氧处理后,检测活性氧(ROS)、线粒体膜电位(MMP)、线粒体膜通透性转换孔(MPTP)开放程度、腺苷三磷酸(ATP)、丙二醛(MDA)、乳酸脱氢酶(LDH)和肌酸激酶(CK)的变化。将大鼠随机分为假手术组,模型组,槲皮素高、中、低剂量组(100、50、25 mg/kg)和阳性对照组(曲美他嗪6.3 mg/kg),每组8只,灌胃相应药物,每天1次,连续7 d;大鼠末次给药后,通过冠状动脉左前降支结扎建立心肌缺血模型,检测血清中LDH、MDA、肌酸激酶同工酶MB(CK-MB)、超氧化物歧化酶(SOD)、线粒体呼吸链复合物Ⅰ(complexⅠ)、complexⅣ和ATP的含量。结果与模型组比较,槲皮素高、中、低剂量组和阳性对照组细胞中ROS荧光强度、MPTP开放程度和CK、LDH、MDA含量均显著降低,MMP和ATP含量均显著升高(P<0.01);槲皮素高、中、低剂量组和阳性对照组大鼠血清中CK-MB、LDH和MDA含量均显著降低,SOD、complexⅠ、complexⅣ和ATP(阳性对照组除外)含量均显著升高(P<0.05或P<0.01)。结论槲皮素能有效减轻心肌缺氧损伤,促进内源性能量的生成,改善心肌缺血后线粒体功能。

从肝治心组方对氧糖剥夺/复灌H9c2心肌细胞模型铁代谢的调节作用

目的研究大鼠心肌缺血/再灌注(myocardial ischemia/reperfusion,MI/R)损伤后心肌细胞的铁代谢及从肝治心组方干预对铁死亡的调节作用。方法选择体外培养的大鼠H9c2心肌细胞,并采用氧糖剥夺/复灌(oxygen glucose deprivation/reperfusion,OGD/R)法建立体外MI/R模型。将细胞分为正常组、模型组、中药组、抑制剂组、激动剂组、联合组、空白血清组。除正常组外,其余各组均予以OGD/R诱导损伤,在复灌时分别给予完全培养基、含15%含药血清的高糖DMEM培养基、含铁死亡抑制剂Ferrostatin-1(Fer-1)(0.5μmol/L)的完全培养基、含爱拉斯汀(Erastin)(10μmol/L)的完全培养基、含Erastin(10μmol/L)的15%含药血清培养基、含15%空白血清的高糖DMEM培养基。采用CCK-8检测细胞存活率,TMRE荧光探针检测线粒体膜电位,FerroOrange检测细胞内Fe^(2+)水平,DCFH-DA荧光探针检测活性氧(reactive oxygen species,ROS)水平。结果与正常组比较,模型组与空白血清组细胞存活率及线粒体膜电位显著下降(P<0.01),Fe^(2+)及ROS水平显著升高(P<0.01)。模型组与空白血清组线粒体膜电位、Fe^(2+)水平差异无统计学意义(P>0.05)。与模型组比较,中药组及抑制剂组细胞存活率及线粒体膜电位显著升高(P<0.01),Fe^(2+)及ROS水平显著降低(P<0.01)。中药组与抑制剂组线粒体膜电位、Fe^(2+)及ROS水平差异无统计学意义(P>0.05)。与模型组相比,激动剂组细胞存活率及线粒体膜电位显著下降(P<0.01),Fe^(2+)及ROS水平显著升高(P<0.01)。与激动剂组相比,联合组细胞存活率及线粒体膜电位显著升高(P<0.01),Fe^(2+)及ROS水平显著降低(P<0.01)。结论从肝治心组方可以减少MI/R损伤,其机制可能与调节心肌细胞铁代谢、抑制铁死亡有关。

靶向CD36调控脂质代谢:糖尿病心肌病防治新靶点

脂质代谢异常诱发心肌结构和功能紊乱,进而导致糖尿病心肌病(DCM)的形成,已成为当前DCM研究的热点。CD36是主要的脂质跨膜转运蛋白,参与调节心脏脂质代谢,在DCM导致心肌损伤的分子机制中具有关键作用。本文总结了CD36的结构及其在特定细胞类型中的作用,并进一步探讨CD36在DCM中的病理生理作用,以及CD36作为靶点的潜在药物治疗策略。

心肌缺血再灌注损伤的代谢组学研究进展

心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)作为心肌梗死后血管重建不良后果的主要原因,严重影响患者的远期疗效,因其致病机制复杂,是临床治疗的难点。随着代谢组学的广泛应用和快速发展,越来越多的研究表明MIRI的发生可能与心肌能量代谢障碍有关,且涉及糖代谢、脂质代谢、氨基酸代谢等多种代谢途径。近年来,对MIRI能量代谢及中西医治疗有关的代谢组学研究已取得一定进展,现将其阐述如下,以期为MIRI临床治疗和研究提供新的思路。

益气活血药方对心肌缺血再灌注损伤模型大鼠氧化应激及线粒体能量代谢的影响

目的研究益气活血药方对心肌缺血再灌注损伤后模型大鼠氧化应激及线粒体能量代谢的影响。方法将50只SD大鼠随机分为假手术组、模型组、益气活血药组、氯喹组、益气活血药+氯喹组,每组10只,除假手术组外,其余各组均采用左冠状动脉前降支结扎法构建心肌缺血再灌注损伤模型,假手术组于左冠状动脉前降支行穿线处理不进行结扎。益气活血药组于造模后次日按8.2 g/(kg·d)予益气活血药液灌胃;氯喹组在造模前30 min腹腔注射10 mg/kg氯喹,造模后次日予2 mL无菌蒸馏水灌胃;益气活血药+氯喹组在造模前30 min腹腔注射10 mg/kg氯喹,造模后次日按8.2 g/(kg·d)予益气活血药液灌胃;模型组和假手术组均于术后次日给予2 mL无菌蒸馏水灌胃,各组均连续灌胃4周。比较各组心功能指标左室舒张末期内径(LVEDd)、左室收缩末期内径(LVESd)、左室射血分数(LVEF)、左室短轴缩短率(LVFS)水平变化情况,比较各组心肌组织氧化应激指标活性氧(ROS)、过氧化氢酶(CAT)、总抗氧化能力(T-AOC)水平变化情况,比较各组心肌细胞能量代谢指标三磷酸腺苷(ATP)、钠离子(Na^(+))-钾离子(K+)-ATP酶和钙离子(Ca^(2+))-ATP酶水平变化情况。结果与假手术组大鼠比较,模型组大鼠心功能指标LVEDd、LVESd均升高(P<0.05),LVFS、LVEF均降低(P<0.05);与模型组比较,益气活血药组及益气活血药+氯喹组大鼠心功能指标LVEDd、LVESd均降低(P<0.05),LVFS、LVEF均升高(P<0.05);与益气活血药组比较,氯喹组及益气活血药+氯喹组大鼠心功能指标LVEDd、LVESd水平均升高(P<0.05),LVFS、LVEF水平均降低(P<0.05)。与假手术组比较,模型组大鼠心肌组织ROS水平升高(P<0.05),CAT、T-AOC水平均降低(P<0.05);与模型组比较,益气活血药组及益气活血药+氯喹组大鼠心肌组织ROS水平均降低(P<0.05),CAT、T-AOC水平均升高(P<0.05);与益气活血药组比较,氯喹组及益气活血药+氯喹组大鼠心肌组织ROS水平均升高(P<0.05),CAT、T-AOC水平均降低(P<0.05)。与假手术组比较,模型组大鼠心肌细胞ATP、Na^(+)-K+-ATP酶、Ca^(2+)-ATP酶水平均降低(P<0.05);与模型组比较,益气活血药组及益气活血药+氯喹组大鼠心肌细胞ATP、Na^(+)-K+-ATP酶、Ca^(2+)-ATP酶水平均升高(P<0.05);与益气活血药组比较,氯喹组及益气活血药+氯喹组大鼠心肌细胞ATP、Na^(+)-K+-ATP酶、Ca^(2+)-ATP酶水平均降低(P<0.05)。结论益气活血药方对心肌缺血再灌注损伤具有保护作用,可明显促进心功能恢复,其作用机制可能与提高心肌抗氧化能力,改善线粒体功能和能量代谢有关。

Metabolic risk factors associated with sudden cardiac death(SCD)during acute myocardial ischemia

Sudden cardiac death(SCD)is the leading cause of death worldwide.Myocardial ischemia(MI)is the most common underlying causal disorder for SCD.Metabolic risks leading to SCD during acute MI are still not fully understood.Here,using tissue metabolomics,we aimed to investigate myocardial metabolic alterations relevant to SCD events in an acute MI rat model induced by coronary artery ligation(CAL).Thirty-four rats were successfully performed CAL,of which 13 developed lethal ventricular tachyarrhythmia(LVTA)-SCD and 7 developed severe atrioventricular block(AB)-SCD.Fourteen rats that survived within 70 min after the ligation were served as peer controls.The partial least squares-discriminant analysis plots demonstrated clear separations between the SCD rats and controls,indicating obvious differences in myocardial metabolome between these rats.The levels of isoleucine,lactate,glutamate choline,phosphorylcholine,taurine and asparagine in ischemic myocardia were positively associated with LVTA-SCD events;in contrast,the levels of alanine,urea,phenylalanine,linoleic acid,elaidic acid and stearic acid were inversely correlated with LVTA-SCD events.The levels of glutamate and urea were positively and negatively relevant to AB-SCD events,respectively.The dangerous metabolites indicated that lower levels of energy substrates,severe hypoxia,the inhibition of transamination and hyper sympathetic excitement and reactive oxygen species in myocardia were vulnerable to SCD during acute MI.The results suggest fatal metabolic alterations correlated with SCD events during acute MI,which could offer novel clues for the prevention or treatment of acute MI-related SCD.

刺五加叶皂苷对大鼠心肌缺血再灌注损伤的保护作用

目的 :观察刺五加叶皂苷 (ASS)对大鼠心肌缺血再灌注损伤的保护作用。方法 :采用在体大鼠结扎冠状动脉前降支 3 0min后 ,松扎再灌注 12 0min造成心肌缺血再灌注模型 ,计算心肌梗死范围 (MIS) ,测定血清磷酸肌酸激酶 (CK)、乳酸脱氢酶 (LDH)、超氧物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH Px)活性及脂质过氧化物 (LP0 )含量 ,血浆内皮素 (ET)、血管紧张素Ⅱ (AngⅡ )、前列环素 (PGI2 )及血栓素A2 (TXA2 )水平。同时测心肌梗死及非梗死区游离脂肪酸 (FFA)含量。结果 :ASS对心肌缺血 3 0min再灌注损伤 12 0min大鼠 ,可明显缩小MIS ,降低血清CK ,LDH活性及LPO含量 ,提高SOD及GSH Px活性 ,能使血浆ET ,AngⅡ ,TXA2 水平明显下降 ,PGI2 水平及PGI2 TXA2比值明显增高 ,亦可使心肌梗死及非梗死区FFA含量明显降低。结论 :ASS对大鼠心肌缺血再灌注损伤具有明显保护作用 ,可能与其增强抗氧化酶活性 ,减少自由基对心肌的氧化损伤 ,纠正心肌缺血时FFA代谢紊乱 ,减少内源性血管活性物质ET及AngⅡ释放 ,纠正PGI2 TXA2

丹参酮、纳络酮对缺血再灌注心肌局部血流量的影响

目的：观察丹参酮、纳络酮对缺血再灌注心肌局部血流量的影响。方法：用结扎冠状动脉左前降支的方法复制犬心肌缺血再灌注模型，心肌局部血流量用氢气清除法测定。结果：丹参酮、纳络酮均能明显增加正常及部分再灌注心肌血流量，丹参酮主要增加缺血周围区血流量，纳络酮可增加缺血中心区及周围区血流量。结论：丹参酮、纳络酮均能缩小缺血区范围，纳络酮还能减轻缺血程度。

三七总皂甙对犬心肌的保护作用

目的：应用犬低温体外循环灌注模型，评价在心脏停跳液中添加三七总皂甙（ＰＮＳ）的心肌保护作用。方法：实验犬１８只，雌雄不分，随机分为３组（每组６只）。１组为对照组，用冷钾停跳液，２组为ＰＮＳ（５０ｍｇ／Ｌ）小剂量组，３组为ＰＮＳ（１５０ｍｇ／Ｌ）大剂量组。结果：心功能指标恢复百分数，超氧化物歧化酶和脂质过氧化产物丙二醛生成，肌酸激酶及其同工酶活力３组比较：１组缺血再灌注后心功能恢复较差，超氧化物歧化酶明显下降（Ｐ＜０．０１），丙二醛及心肌酶明显升高（Ｐ＜０．０１），２组、３组则变化不明显（Ｐ＞０．０５）。１组与２组、３组比较有显著差异（Ｐ＜０．０１），２、３组间亦有显著差异（Ｐ＜０．０１）。心肌超微结构的保护１组最差，３组最好。结论：在心脏停跳液中加较小剂量的ＰＮＳ具有良好的心肌保护作用，加大剂量效果更佳。

羟基红花黄色素A对犬急性心肌缺血的保护作用

目的研究羟基红花黄色素A(HSYA)对犬急性心肌缺血的保护作用。方法采用结扎冠状动脉前降支的方法,造成犬急性实验性心肌缺血模型;超声多普勒方法测定心肌血流量;通过血氧分析研究心肌氧代谢;放射免疫法测定血浆内皮素(ET)的含量;用心外膜电图描记和定量组织化学染色方法计算心肌缺血程度、范围及梗死面积。结果HSYA可以增加心肌血流量以及冠状静脉窦内的血氧含量,并可以抑制ET从受损微小血管的释放,而且HSYA可以减弱心肌缺血的程度和范围,缩小缺血的面积。结论HSYA可以抑制ET的释放,增加心肌血流量,改善心肌氧代谢,抑制心肌缺血损伤。

体外反搏对心肌缺血犬血流动力学的影响及内皮素机制的探讨

目的:探讨体外反搏改善心肌缺血犬血流动力学的作用和内皮素机制。方法:19只健康杂种犬随机分为对照组、缺血组和反搏组,分别于冠状动脉左前降支结扎前和结扎后60MIN、120 MIN、180 MIN记录以下指标: ①主动脉根部血压;②左心室收缩和舒张末压、+DP/DTMAX和-DP/DTMAX;③头臂干血流量;④放免法检测血浆和心肌内皮素-1(ET-1)的含量。结果:冠脉结扎1 H,缺血组和反搏组犬血压、左心室收缩和舒张功能、头臂干血流量明显低于正常组(P<0．05),而血浆ET-1水平明显高于正常组(P<0．05)。经过体外反搏2 H,反搏组犬的收缩压、舒张压和平均压、左心室收缩和舒张功能、头臂干血流量明显高于缺血组(P<0．05);而反搏组犬的血浆和心肌ET-1 水平明显低于缺血组(P<0．05)。结论:体外反搏可改善心肌缺血犬血流动力学指标,其机制可能与降低ET-1的产生有关。

山楂叶总黄酮对麻醉犬冠脉结扎所致心肌缺血的保护作用

目的观察山楂叶总黄酮对麻醉犬冠脉结扎所致心肌缺血的保护作用。方法结扎麻醉犬冠脉复制心肌缺血模型。观察给药后ST段偏移总和(∑-ST)、ST段抬高≥2mV的个数(N-ST)和乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)的变化。通过TTC染色,观察心脏梗塞范围。结果山楂叶总黄酮可显著减少冠脉结扎所致的∑-ST抬高和N-ST增加,同时减少血清中LDH和CK的释放,缩小心肌梗塞范围。结论山楂叶总黄酮能明显减轻心肌缺血程度。

犬急性心肌梗死晚期再灌注对心肌Fas/FasL系统的影响及其可能的氧化应激机制

目的:探讨急性心肌梗死晚期再灌注对心肌细胞凋亡基因Fas/FasL表达的影响及其可能的氧化应激机制。方法:18条健康成年杂种犬,按随机方法分为3组,每组6条。晚期再灌注组:结扎冠状动脉前降支6 h后再灌注6 h;持续缺血组:开胸后6 h,结扎冠状动脉前降支6 h,不行再灌注处理;对照组:冠状动脉前降支只穿线不结扎持续12 h。免疫组化法检测梗死边缘区心肌Fas和FasL蛋白表达,TUNEL法测心肌细胞凋亡指数(AI),比色法测定心肌超氧化物歧化酶(SOD)活性、还原性谷胱甘肽酶(GR)活性、丙二醛(MDA)含量等。结果:心肌Fas和FasL蛋白表达以及细胞凋亡指数在持续缺血组和晚期再灌注组明显高于对照组(分别为P<0.05,P<0.01),而且晚期再灌注组明显高于持续缺血组(P<0.05)。持续缺血组和晚期再灌注组的心肌细胞SOD活性和GR活性明显低于对照组(分别为P<0.05,P<0.01),而MDA含量均明显高于对照组(P<0.05),并且两组之间亦有显著差别(P<0.05)。结论:AM I晚期再灌注使梗死边缘区心肌细胞Fas/FasL蛋白表达以及细胞凋亡指数增加,提示晚期再灌注仍然存在再灌注损伤,其机制可能与氧化应激有关。

黄芪总皂苷对异丙肾上腺素致大鼠心肌损伤的保护作用

目的研究黄芪总皂苷(astragalosides,AS)对异丙肾上腺素(isoproterenol,ISO)致大鼠心肌损伤的影响及机制。方法用AS(5mg·kg-1·d-1×7d,ip)或曲美他嗪(10mg·kg-1·d-1×7d,ip)等治疗ISO(5mg·kg-1·d-1×2d,sc)心肌损伤大鼠,观察心肌组织病理改变并测定心肌组织乳酸、丙二醛及高能磷酸化物ATP,ADP和AMP含量。结果AS组心肌组织病理分级接近曲美他嗪对照治疗组,心肌乳酸和丙二醛含量较模型组显著降低(分别为P<0·05,P<0·01),ATP含量增加(P<0·05),ADP含量降低(P<0·05),AMP含量有增加趋势,以上治疗指标与曲美他嗪组比较无显著差异(P>0·05)。结论AS可拮抗ISO引起的大鼠心肌损伤,其机制与改善心肌能量代谢、抑制脂质过氧化有关。