线粒体,心脏

摘要： 背景:慢性心力衰竭与心肌线粒体稳态异常以及心肌能量代谢紊乱等密切相关。解偶联蛋白2是位于线粒体内膜上的质子泵,与心肌的氧化应激、能量代谢和细胞凋亡关系密切,在慢性心力衰竭病理生理过程中起着极其重要作用。目的:总结鸢尾素对慢性心力衰竭的影响,讨论有氧运动通过鸢尾素改善慢性心力衰竭的机制。方法:应用计算机检索PubMed和CNKI等数据库从2001年至2018年收录的与鸢尾素和慢性心力衰竭相关的文献。英文检索词为:“aerobic exercise”,“Irisin”,“chronic heart failure”,中文检索词为:“有氧运动”,“鸢尾素”,“慢性心力衰竭”。排除无关和重复文献,最后纳入53篇文章进行分析总结,包括8篇中文和45篇英文文献。结果与结论:鸢尾素可抑制活性氧生成,可以模拟有氧运动带来的良好效益,在有氧运动改善慢性心力衰竭中起着重要的作用,因此鸢尾素可作为运动治疗心力衰竭的潜在靶点。长期的有氧运动可能通过鸢尾素/活性氧/解耦联蛋白2途径改善心力衰竭过程。

摘要： Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mito-KATP) channels in urocortin postconditioning-induced protection of rat cardiomyocytes.Methods Clean-grade healthy male Sprague-Dawley rats,aged 16-20 weeks,weighing 200-250 g,were used in this study.Cardiomyocytes of rats were isolated,cuhured and divided into 4 groups (n =28 each) using a random number table method:control group (group C),H/R group (group HR),urocortin postconditioning group (group U) and 5-hydroxydecanoate (5-HD,mito-KAw channel blocker) plus urocortin postconditioning group (group HU).In group C,the cells were continuously cultured for 150 min in an incubator filled with 95％ O2-5％ CO2 at 37 °C.In group HR,the cells were exposed to 40-min hypoxia in an incubator filled with 95％ N2-5％ CO2 at 37 °C,followed by 110-min reoxygenation.In group U,the cells were exposed to 40-min of hypoxia,followed by 10-min reoxygenation,and then cultured in a cuhure medium containing 10-8mmol/L urocortin for 30 min,followed by 70-min reoxygenation.In group HU,the cells were cultured for 10 min in a culture medium containing 10-4mmol/L 5-HD,and the other treatments were similar to those previously described in group U.At the end of reoxygenation,the opening of mitochondrial permeability transition pore (mPTP) and mitochondrial membrane potential (MMP) were measured by fluorescence spectrophotometry.The expression of Bax and Bcl-2 was determined by Western blot,and the cell viability was measured by CCK-8 assay.Results Compared with group C,the viability of cardiomyocytes and MMP were significantly decreased,the opening of mPTP was increased,the expression of Bcl-2 was down-regulated,and the expression of Bax was up-regulated in the other 3 groups (P＜0.05).Compared with group HR,the viability of cardiomyocytes and MMP were significantly increased,the opening of mPTP was decreased,the expression of Bcl-2 was up-regulated,and the expression of Bax was down-regulated in group U,and the opening of mPTP was decreased (P ＜ 0.05),and no significant change was found in the other parameters in group HU (P＞0.05).Compared with group U,the viability of cardiomyocytes and MMP were significantly decreased,the opening of mPTP was increased,the expression of Bcl-2 was down-regulated,and the expression of Bax was up-regulated in group HU (P＜0.05).Conclusion The mechanism by which urocortin postconditioning attenuates H/R-induced damage to rat cardiomyocytes is associated with promoting mito-KATP channel opening and inhibiting mPTP opening.%目的 评价线粒体ATP敏感性钾(mtio-KATP)通道在尿皮质素后处理对大鼠心肌细胞保护效应中的作用.方法 清洁级健康雄性SD大鼠,16～20周龄,体重200～250 g,分离培养心肌细胞,采用随机数字表法将心肌细胞分成4组(n=28):对照组(C组)、缺氧复氧组(HR组)、尿皮质素后处理组(U组)和mito-KATP通道阻滞剂5-羟葵酸(5-HD)+尿皮质素后处理组(HU组).C组:在37°C95％ O2-5％ CO2培养箱中持续培养150 min;HR组:在37°C95％ N2-5％ CO2培养箱中缺氧40min后,复氧110 min;U组:缺氧40 min后先复氧10 min,然后在含10-8 mmol/L尿皮质素的培养基中孵育30 min,再复氧70 min;HU组:采用含10-4 mmol/L 5-HD的培养基孵育10 min,随后处理同U组.于复氧结束时,采用荧光法检测线粒体通透性转换孔(mPTP)开放程度以及线粒体膜电位(MMP).采用Western blot法检测Bax和Bcl-2表达,采用CCK-8法检测细胞活力.结果 与C组比较,其余3组心肌细胞活力和MMP降低,mPTP开放程度升高,Bcl-2表达下调,Bax表达上调(P＜0.05);与HR组比较,U组心肌细胞活力和MMP升高,mPTP开放程度降低,Bcl-2表达上调,Bax表达下调,HU组mPTP开放程度降低(P＜0.05),其余指标差异无统计学意义(P＞0.05);与U组比较,HU组心肌细胞活力和MMP降低,mPTP开放程度升高,Bcl-2表达下调,Bax表达上调(P＜0.05).结论 尿皮质素后处理对大鼠心肌细胞保护效应的全部机制与促进mito-KATP通道开放有关.

摘要： 目的:探讨钾通道开放剂尼可地尔对离体大鼠心肌缺血再灌注损伤(MIRI)的影响.方法:建立Langendorff离体心脏灌流系统,44只大鼠随机分为4组:正常组、缺血再灌注组(I-R组)、腺苷(100μmol/L)缺血再灌注组(A/I-R组)、尼可地尔(200μmol/L)缺血再灌注组(N/I-R组),每组11只.分别记录并分析各组左心室发展压(LVDP)、左心室内压力最大上升/下降速率(±dp/dtmax)、再灌注心律失常(RA)、心肌梗死面积以及左心室心肌组织的乙醛脱氢酶2(ALDH2)、抗凋亡基因B淋巴细胞瘤-2(Bcl-2)以及促凋亡基因B淋巴细胞瘤-2相关x蛋白(Bax)的表达水平.结果(:1)N/I-R组再灌注30 min与再灌注45 min的LVDP均高于I-R组与A/I-R组(P均0.05).结论:尼可地尔可以减少MIRI,对心肌起到保护作用,其总体作用效果优于腺苷.尼可地尔可上调线粒体ALDH2、Bcl-2表达以及下调Bax的基因蛋白的表达.%Objective: To investigate the effect of potassium channel opener nicorandil on myocardial ischemia-reperfusion injury (MIRI) in isolated rat's heart. Methods: Langendorff system was established for isolated heart reperfusion. A total of 44 rats were randomly divided into 4 groups: Normal control group, Ischemia-reperfusion (I-R) group, Adenosine/I-R (A/I-R) group, the I-R heart was treated by adenosine 100 μmo/L and Nicorandil/I-R (N/I-R) group, the I-R heart was treated by nicorandil 200 μmo/L.n=11 in each group. Left ventricular developed pressure (LVDP), the maximal rise/fall rate of left ventricular pressure (±dp/dtmax), reperfusion arrhythmia (RA) and myocardial infarction (MI) size were recorded; the expressions of left ventricular tissue acetaldehyde dehydrogenase 2 (ALDH2), Bcl-2 and Bax were examined and compared among different groups. Results:①Compared with I-R and A/I-R groups, N/I-R group had increased LVDP at 30 min and 45 min reperfusion, allP0.05. Conclusion: Nicorandil may reduce MIRI and protect myocardium in isolated rat's heart, the overall effect is better than adenosine. Nicorandil can up-regulate the expressions of mitochondrial ALDH2, Bcl-2 and down-regulate the expression of Bax.

摘要： Objective To evaluate the relationship between the mechanism of silent information regulator factor 2-related enzyme 1 (SIRT1)-mediated mitophagy in the myocardium and mitofusin 2 (Mfn2) in diabetic rats.Methods Twenty-four SPF healthy adult male Sprague-Dawley rats,weighing 210-220 g,were allocated into 3 groups (n =8 each) using a random number table:control group (group C),diabetes mellitus group (group DM) and diabetes mellitus plus SIRT1 activator SRT1720 group (group DM+SRT).Diabetes mellitus was induced by intraperitoneal 1％ streptozotocin 60 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L 3 days later.SRT1720 1 mg/kg was injected via the caudal vein for 7 consecutive days in group DM+SRT.The ultrasonic method was used to measure the parameters of heart function including left ventricular end-diastolic volume (LVEDV),left ventricular end-systolic volume (LVESV),left ventricular ejection fraction (LVEF),heart rate (HR),E wave velocity (E),A wave velocity (A) and E/A ratio.Myocardial specimens were obtained for determination of the interaction between SIRT1 and Mfn2 and acetylation of Mfn2 (by co-immuno-precipitation) and expression of SIRT1,Mfn2,microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ),LC3 Ⅰ,Beclin1 and P62 (by Western blot).The ratio LC3 Ⅱ to LC3 Ⅰ (LC3 Ⅱ / Ⅰ ratio) was calculated.Results Compared with group C,LVEDV,LVEF,HR,E and E/A ratio were significantly decreased,A was increased,LC3 Ⅱ / Ⅰ ratio was decreased,the expression of Beclin1,SIRT1 and Mfn2 was down-regulated,the expression of P62 was up-regulated,and the interaction between SIRT1 and Mfn2 was decreased in group DM (P＜0.05).Compared with group DM,LVEDV,LVEF,E and E/A ratio were significantly increased,A was decreased,LC3 Ⅱ / Ⅰ ratio was increased,the expression of Beclin1 and SIRT1 was up-regulated,the expression of P62 was down-regulated,the interaction between SIRT1 and Mfn2 was increased,and the acetylation of Mfn2 was decreased in group DM+SRT (P＜0.05).Conclusion The mechanism by which SIRT1 mediates mitophagy in the myocardium is related to SIRT1-induced deacetylation of Mfn2 in diabetic rats.%目的 评价沉默调节蛋白1(SIRT1)介导糖尿病大鼠心肌线粒体自噬的机制与线粒体融合蛋白2(Mfn2)的关系.方法 SPF级健康成年雄性SD大鼠24只,体重210～220 g,采用随机数字表法分为3组(n=8):对照组(C组)、糖尿病组(DM组)、糖尿病+SIRT1激动剂SRT1720组(DM+SRT组).采用腹腔注射1％链脲佐菌素60 mg/kg的方法建立大鼠糖尿病模型.DM+SRT组连续7d尾静脉注射SIRT1激动剂SRT1720 1 mg/kg.随后采用超声法测定心功能指标:左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV)、左室射血分数(LVEF)、心率(HR)、舒张早期心室充盈速度最大值(E)、舒张晚期心室充盈速度最大值(A)和峰值流速比值(E/A比值);取心肌组织,采用免疫共沉淀法检测SIRT1与Mfn2的结合水平、Mfn2乙酰化水平;Western blot法检测SIRT1、Mfn2、微管相关蛋白1轻链3Ⅱ(LC3Ⅱ)、LC3 Ⅰ、Beclin1和P62的表达,计算LC3Ⅱ与LC3 Ⅰ的比值(LC3Ⅱ/Ⅰ).结果 与C组比较,DM组LVEDV、LVEF、HR、E和E/A比值降低,A升高,LC3Ⅱ/Ⅰ比值降低,Beclin1、SIRT1和Mfn2表达下调,P62表达上调,Mfn2-SIRT1结合水平降低(P＜0.05).与DM组比较,DM+SRT组LVEDV、LVEF、E和E/A比值升高,A降低,LC3Ⅱ/Ⅰ比值升高,Beclin1和SIRT1表达上调,P62表达下调,Mfn2-SIRT1结合水平升高,Mfn2乙酰化水平降低(P＜0.05).结论 SIRT1介导糖尿病大鼠心肌线粒体自噬的机制与其对Mfn2的去乙酰化作用有关.

摘要： Objective To observe the expression of Drp1 in the cardial muscle tissue of diabetic mice and nor-mal mice.Methods Nine male db /db mice were randomly divided into 3 groups(db /db 6week group,db /db 12week group and db /db 18week group).Nine male normal mice were randomly divided into another 3 groups(wt 6week group, wt 12week group and wt 18week group).The expression of Drp1 was detected by real-time PCR,Western Blot and im-munohistochemical.Results Compared to the normal group,the expression of Drp1 was decreased obviously in db /db mice group,and was gradually decreased with age.Conclusions The decreased expression of Drp1 maybe is one of the possible mechanisms of diabetic cardiomyopathy.%目的：观察 db ／db 糖尿病小鼠与正常小鼠心肌组织中动力相关蛋白1（Drp1）表达水平的变化。方法9只雄性 db ／db 糖尿病小鼠，随机分为6周组（db ／db 6week），12周组（db ／db 12week），18周组（db ／db 18week）；另设健康组雄性小鼠9只，随机分为6周组（wt 6week），12周组（wt 12week），18周组（wt 18week），每小组3只。分别利用实时定量 PCR，Western Blot，免疫组织化学的方法检测心肌组织中 Drp1的表达和定位。结果db ／db 糖尿病小鼠分组中 Drp1的表达低于健康组，且随年龄的增长表达逐渐降低。结论糖尿病小鼠中Drp1表达进行性的降低，引起线粒体分裂异常从而导致线粒体的生物功能障碍，可能是糖尿病心肌病发生及发展的重要机制之一。

摘要： 背景：短期高强度间歇运动训练是否能改善心肌梗死后心脏功能及其相关作用机制尚不清楚。目的：观察高强度间歇运动训练对心肌梗死后心脏功能及线粒体含量的影响,并探讨线粒体自噬和生物合成在其中的生物效应。方法：选取雄性SD大鼠制备急性心肌梗死模型,术后1周进行高强度间歇运动训练,训练方案为：以80%最大摄氧量快速跑4 min,间歇以40%最大摄氧量慢速跑3 min,重复7个循环,5 d/周,共4周。结果与结论：4周高强度间歇运动训练显著提高急性心肌梗死后左心室泵功能和线粒体含量,增加线粒体膜电位和ATP合成活力,抑制线粒体活性氧产生,上调PGC-1α/Tfam介导的线粒体生物合成和Bnip3/Beclin-1介导线粒体自噬。结果表明短期高强度间歇运动训练即可提高急性心肌梗死后心肌健康线粒体含量,从而改善心肌能量代谢和舒缩功能,是一种时效性较强的心脏康复手段。

摘要： 目的 探讨不同强度运动对大鼠心肌线粒体解偶联蛋白2(UCP2)表达的影响及其与心肌能量变化的关系.方法 雄性Wistar大鼠45只,随机分为安静对照组,渐进训练组、渐进训练力竭组,每组15只.4周后,测定血清游离脂肪酸(FFA)浓度及心肌线粒体三磷酸腺苷(ATP)含量,反转录聚合酶链反应(RT-PCR)及Western blotting测定心肌线粒体UCP2的表达变化.结果 渐进训练力竭组ATP含量明显低于安静对照组与渐进训练组(P＜0.01);渐进训练力竭组血清FFA浓度明显升高,分别是安静对照组和渐进训练组的2.0倍和1.7倍(P＜0.01).RT-PCR及Western blotting结果显示,与安静对照组及渐进训练组相比,渐进训练力竭组心肌线粒体UCP2 mRNA和蛋白表达明显升高(P＜0.01).相关性分析显示,心肌线粒体UCP2的表达与血清FFA浓度呈正相关(r=0.795,P＜0.01),而与ATP含量呈负相关(r=-0.843,P＜0.01).结论 力竭运动训练可引起大鼠血清FFA浓度升高及心肌线粒体ATP含量降低,同时可诱导心肌线粒体UCP2表达.UCP2的表达与FFA浓度呈正相关,而与ATP含量呈负相关,提示UCP2可能参与了力竭运动中心的肌能量代谢.

摘要： 线粒体功能的改变和衰老与诸多遗传或后天获得的疾病有关。基因靶向技术的突破使基因工程小鼠模型的发展呈现了多样性,这些模型有助于研究线粒体生物发生、代谢和功能障碍。由于心脏需要持续和巨大的能量以满足＂循环泵＂的功能,因此线粒体对于成人心脏正常功能显得尤为重要。

摘要： 线粒体生理和病理学研究正日益引起人们的重视。线粒体功能的改变和衰老与很多先天和后天获得的疾病相关。对于心脏而言,由于正常心脏需要持续和巨大的能量以满足＂循环泵＂的功能[1],因此＂动力工厂＂线粒体的作用尤为重要。本文对心肌病中线粒体功能的改变及分子基础进行综述,为阐明线粒体能量代谢功能在心肌病中发挥的作用及其分子调控机制奠定基础。

摘要： 一种离体灌流心脏活性氧族和线粒体膜电位的检测方法，通过离体灌流心脏缺血再灌注模型的建立，实现将离体心脏灌流系统与探针负载装置及激光共聚焦显微镜的关联，进而进行活性氧族和线粒体膜电位的荧光探针的实时负载和显微镜成像，最后通过图像处理和数据分析，本发明能够对稳定灌流状态下以及以急性超负荷、缺血再灌注等为代表的多种离体心脏模型中心脏ROS和线粒体膜电位进行实时、定位测量。本发明具有直接、准确、可见、时间和空间定位，与搏动心脏代谢与功能同步测量的特点，而且成本低，效率高，可信度与重复性好。

摘要： 本发明涉及利用人线粒体腺苷酸激酶同工酶的用于心脏病的免疫制剂和诊断试剂盒。本发明提供了用于心脏病的免疫制剂和诊断试剂盒，其特征在于利用了存在于肌肉细胞中的心肌细胞但不存在于骨骼肌细胞中的腺苷酸激酶同工酶作为心脏病的诊断标记，因此能够更正确和容易地诊断心脏病。

摘要： 本发明证明，线粒体DNA损伤的发生先于动脉粥样硬化损伤的发展，或与之同步；主动脉线粒体DNA损伤随年龄增加；而且，基因型和饮食都会影响线粒体DNA损伤程度。因此，本发明证明，线粒体DNA损伤发生于动脉粥样硬化的早期，可能是动脉粥样硬化形成的引发因素，并基于此提供了一种根据线粒体DNA损伤量来预报冠状动脉粥样硬化性心脏病的方法。

摘要： 本申请提供了使用RNAi技术，特别是用siRNA沉默细胞中线粒体基因表达，或清除细胞中线粒体基因表达产物的方法，应用和相应药物。实验结果表明，使用相应siRNA可以有效敲低线粒体中所有基因表达，并且恢复突变线粒体基因带来的功能缺失或损害。

摘要： 一种离体灌流心脏活性氧族和线粒体膜电位的检测方法，通过离体灌流心脏缺血再灌注模型的建立，实现将离体心脏灌流系统与探针负载装置及激光共聚焦显微镜的关联，进而进行活性氧族和线粒体膜电位的荧光探针的实时负载和显微镜成像，最后通过图像处理和数据分析，本发明能够对稳定灌流状态下以及以急性超负荷、缺血再灌注等为代表的多种离体心脏模型中心脏ROS和线粒体膜电位进行实时、定位测量。本发明具有直接、准确、可见、时间和空间定位，与搏动心脏代谢与功能同步测量的特点，而且成本低，效率高，可信度与重复性好。

摘要： 本发明证明,线粒体DNA损伤的发生先于动脉粥样硬化损伤的发展,或与之同步;主动脉线粒体DNA损伤随年龄增加;而且,基因型和饮食都会影响线粒体DNA损伤程度。因此,本发明证明,线粒体DNA损伤发生于动脉粥样硬化的早期,可能是动脉粥样硬化形成的引发因素,并基于此提供了一种根据线粒体DNA损伤量来预报冠状动脉粥样硬化性心脏病的方法。

摘要： 本发明涉及利用人线粒体腺苷酸激酶同工酶的用于心脏病的免疫制剂和诊断试剂盒。本发明提供了用于心脏病的免疫制剂和诊断试剂盒,其特征在于利用了存在于肌肉细胞中的心肌细胞但不存在于骨骼肌细胞中的腺苷酸激酶同工酶作为心脏病的诊断标记,因此能够更正确和容易地诊断心脏病。

摘要： 本文提供与反应性脂质物质反应以形成无毒产物或活性产物的化合物。还提供了还原反应性脂质物质的方法。另外提供了在患有线粒体功能障碍的患者中治疗线粒体的方法。在其他实施例中，提供了一种化合物，其与在线粒体中存在的活化剂反应以形成抑制或增强线粒体通透性转化孔(MPTP)的开放的活性产物。在另外的实施例中，提供了抑制或增强MPTP的开放的方法。还提供了能够穿过血脑屏障(BBB)进入中枢神经系统(CNS)的非极性化合物。

摘要： 本公开涉及从细胞获得线粒体的方法，通过此类方法获得的线粒体和通过此类方法获得的线粒体的用途。

摘要： 根据本发明，提供了一种包含具有较小尺寸的线粒体的群体和将线粒体包裹在封闭空间中的基于脂质膜的囊泡的群体的组合物，以及生产所述组合物的方法。