Bafadam Soleyman, Mokhtari Behnaz, Vafaee Manoucheher Seyedi, Oscuyi Zohreh Zavvari, Nemati Samira, Badalzadeh Reza
Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Exp Physiol. 2025 May;110(5):744-754. doi: 10.1113/EP091358. Epub 2024 Mar 13.
Ischaemic heart diseases (IHD) are among the major causes of mortality in the elderly population. Although timely reperfusion is a common treatment for IHD, it causes additional damage to the ischaemic myocardium known as ischaemia-reperfusion (IR) injury. Considering the importance of preventing reperfusion injuries, we aimed to examine the combination effect of mitochondrial transplantation (MT) and coenzyme Q (CoQ) in myocardial IR injury of aged male rats. Seventy-two aged male Wistar rats were randomly divided into six groups: Sham, IR, CoQ, MT, combination therapy (MT + CoQ) and vehicle. Myocardial IR injury was established by occlusion of the left anterior descending coronary artery followed by reopening. Young male Wistar rats were used as mitochondria donors. Isolated mitochondria were injected intraventricularly (500 µL of a respiration buffer containing 6 × 10 ± 5 × 10 mitochondria/mL) in MT-receiving groups at the onset of reperfusion. CoQ (10 mg/kg/day) was injected intraperitoneally for 2 weeks before IR induction. Twenty-four hours after reperfusion, haemodynamic parameters, myocardial infarct size (IS), lactate dehydrogenase (LDH) release and cardiac mitochondrial function (mitochondrial reactive oxygen species (ROS) generation and membrane potential) were measured. The combination of MT and CoQ improved haemodynamic index changes and reduced IS and LDH release (P < 0.05). It also decreased mitochondrial ROS generation and increased membrane potential (P < 0.05). CoQ also showed a significant cardioprotective effect. Combination therapy displayed greater cardioprotective effects than single treatments. This study revealed that MT and CoQ combination treatment can be considered as a promising cardioprotective strategy to reduce myocardial IR injury in ageing, in part by restoring mitochondrial function.
缺血性心脏病(IHD)是老年人群主要的死亡原因之一。尽管及时再灌注是IHD的常见治疗方法,但它会对缺血心肌造成额外损伤,即缺血再灌注(IR)损伤。考虑到预防再灌注损伤的重要性,我们旨在研究线粒体移植(MT)和辅酶Q(CoQ)联合应用对老年雄性大鼠心肌IR损伤的影响。72只老年雄性Wistar大鼠被随机分为六组:假手术组、IR组、CoQ组、MT组、联合治疗组(MT + CoQ)和溶剂对照组。通过结扎左冠状动脉前降支然后再通来建立心肌IR损伤模型。年轻雄性Wistar大鼠用作线粒体供体。在再灌注开始时,向接受MT的组心室内注射分离的线粒体(500 μL含有6×10±5×10个线粒体/mL的呼吸缓冲液)。在诱导IR前2周,腹腔注射CoQ(10 mg/kg/天),持续2周。再灌注24小时后,测量血流动力学参数、心肌梗死面积(IS)、乳酸脱氢酶(LDH)释放以及心脏线粒体功能(线粒体活性氧(ROS)生成和膜电位)。MT和CoQ联合应用改善了血流动力学指标变化,减小了IS并减少了LDH释放(P < 0.05)。它还减少了线粒体ROS生成并增加了膜电位(P < 0.05)。CoQ也显示出显著的心脏保护作用。联合治疗比单一治疗显示出更大的心脏保护作用。本研究表明,MT和CoQ联合治疗可被视为一种有前景的心脏保护策略,以减少衰老过程中的心肌IR损伤,部分原因是通过恢复线粒体功能。