Mokhtari Behnaz, Badalzadeh Reza
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2023 May;50(5):3973-3983. doi: 10.1007/s11033-023-08318-3. Epub 2023 Feb 24.
Aging, as a recognized risk factor for ischemic heart disease, interferes with protective mechanisms and abolishes the optimal effectiveness of cardioprotective interventions, leading to the loss of cardioprotection following myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore the possible interaction of aging with cardioprotection induced by combination therapy with coenzyme Q (CoQ) and mitochondrial transplantation in myocardial I/R injury of aged rats.
Male Wistar rats (n = 72, 400-450 g, 22-24 months old) were randomized into groups with/without I/R and/or CoQ and mitochondrial transplantation, alone or in a combinational mode. An in vivo model of myocardial I/R injury was established by left anterior descending coronary artery occlusion and re-opening. Mitochondria were isolated from donor rats and injected intramyocardially (150 µl of the mitochondrial suspension containing 2 × 10±0.3 × 10 mitochondria) at the onset of reperfusion in recipient groups. CoQ (20 mg/kg/day) was injected intramuscularly for 7 days before I/R operation. Lastly, myocardial function, cTn-I level, expression of autophagy-associated proteins (Beclin1, p62, and LC3-II/LC3-I), and the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were assessed.
Co-application of CoQ and mitotherapy concomitantly improved myocardial function and decreased cTn-I level in aged reperfused hearts (P < .001). This combination therapy also modulated autophagic activity and decreased pro-inflammatory cytokines (P < .01 to P < .001). This combinational approach induced noticeable cardioprotection in comparison with monotherapies-received groups.
We found that combination of CoQ and mitochondrial transplantation attenuated myocardial I/R injury in aged rats, in part by modulating autophagy and inflammatory response, hence, appears to restore aging-related loss of cardioprotection in aged patients.
衰老作为缺血性心脏病公认的危险因素，会干扰保护机制，使心脏保护干预措施无法达到最佳效果，导致心肌缺血/再灌注（I/R）损伤后心脏保护作用丧失。本研究旨在探讨衰老与辅酶Q（CoQ）联合线粒体移植诱导的心脏保护作用在老年大鼠心肌I/R损伤中的可能相互作用。
将雄性Wistar大鼠（n = 72，400 - 450 g，22 - 24月龄）随机分为有/无I/R和/或CoQ及线粒体移植组，单独或联合应用。通过左冠状动脉前降支闭塞和再通建立心肌I/R损伤的体内模型。在再灌注开始时，从供体大鼠分离线粒体并心肌内注射（150 μl含2×10±0.3×10线粒体的线粒体悬液）到受体组。在I/R手术前7天肌肉注射CoQ（20 mg/kg/天）。最后，评估心肌功能、肌钙蛋白I水平、自噬相关蛋白（Beclin1、p62和LC3-II/LC3-I）的表达以及促炎细胞因子（TNF-α、IL-1β和IL-6）水平。
CoQ与线粒体治疗联合应用可同时改善老年再灌注心脏的心肌功能并降低肌钙蛋白I水平（P <.001）。这种联合治疗还调节了自噬活性并降低了促炎细胞因子水平（P <.01至P <.001）。与接受单一疗法的组相比，这种联合方法诱导了显著的心脏保护作用。
我们发现CoQ与线粒体移植联合可减轻老年大鼠心肌I/R损伤，部分是通过调节自噬和炎症反应，因此，似乎可恢复老年患者中与衰老相关的心脏保护作用丧失。
