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线粒体靶向抗氧化剂MitoTEMPO对缺血再灌注所致心脏功能障碍的保护作用:大脑中动脉闭塞性脑卒中模型研究

Protective effect of MitoTEMPO against cardiac dysfunction caused by ischemia-reperfusion: MCAO stroke model study.

作者信息

Akkoca Ahmet, Büyükakıllı Belgin, Ballı Ebru, Gültekin Burcu, Özbay Erkan, Oruç Demirbağ Hatice, Türkseven Çağatay Han

机构信息

Department of Occupational Health and Safety, Taşkent Vocational School, Selcuk University, Konya, Türkiye.

Department of Biophysics, Faculty of Medicine, Mersin University, Mersin, Türkiye.

出版信息

Int J Neurosci. 2024 Dec;134(12):1582-1593. doi: 10.1080/00207454.2023.2273768. Epub 2023 Oct 24.

Abstract

PURPOSE

Neurological impairments are the leading cause of post-stroke mortality, while stroke-related cardiovascular diseases rank second in significance. This study investigates the potential protective effects of MitoTEMPO (2,2,6,6-tetramethyl-4-[[2-(triphenylphosphonio) acetyl] amino]-1-piperidinyloxy, monochloride, monohydrate), a mitochondria-specific antioxidant, against cardiac and neurological complications following stroke. The objective is to assess whether MitoTEMPO can be utilized as a protective agent for individuals with a high risk of stroke.

MATERIALS AND METHODS

Seventeen-week-old male Wistar Albino rats were randomly assigned to three groups: SHAM, ischemia-reperfusion and MitoTEMPO + ischemia-reperfusion (MitoTEMPO injection 0.7 mg/kg/day for 14 days). The SHAM group underwent a sham operation, while the ischemia-reperfusion group underwent 1-h middle cerebral artery occlusion followed by three days of reperfusion. Afterwards, noninvasive thoracic electrical bioimpedance and electrocardiography measurements were taken, and sample collection was performed for histological and biochemical examinations.

RESULTS

Our thoracic electrical bioimpedance and electrocardiography findings demonstrated that MitoTEMPO exhibited a protective effect on most parameters affected by ischemia-reperfusion compared to the SHAM group. Furthermore, our biochemical and histological data revealed a significant protective effect of MitoTEMPO against oxidative damage.

CONCLUSIONS

The findings suggest that both ischemia-reperfusion-induced cardiovascular abnormalities and the protective effect of MitoTEMPO may involve G-protein coupled receptor-mediated signaling mechanisms. This study was conducted with limitations including a single gender, a uniform age group, a specific stroke model limited to middle cerebral artery, and pre-scheduled only one ischemia-reperfusion period. In future studies, addressing these limitations may enable the implementation of preventive measures for individuals at high risk of stroke.

摘要

目的

神经功能障碍是中风后死亡的主要原因,而与中风相关的心血管疾病在重要性方面排名第二。本研究调查了线粒体特异性抗氧化剂MitoTEMPO(2,2,6,6-四甲基-4-[[2-(三苯基膦基)乙酰基]氨基]-1-哌啶氧基,一氯化物,一水合物)对中风后心脏和神经并发症的潜在保护作用。目的是评估MitoTEMPO是否可作为中风高危个体的保护剂。

材料和方法

将17周龄的雄性Wistar白化大鼠随机分为三组:假手术组、缺血再灌注组和MitoTEMPO + 缺血再灌注组(MitoTEMPO注射剂量为0.7 mg/kg/天,共14天)。假手术组进行假手术,缺血再灌注组进行1小时大脑中动脉闭塞,随后再灌注3天。之后,进行无创胸电阻抗和心电图测量,并采集样本进行组织学和生化检查。

结果

我们的胸电阻抗和心电图结果表明与假手术组相比,MitoTEMPO对受缺血再灌注影响的大多数参数具有保护作用。此外,我们的生化和组织学数据显示MitoTEMPO对氧化损伤具有显著的保护作用。

结论

研究结果表明,缺血再灌注诱导的心血管异常和MitoTEMPO 的保护作用可能都涉及G蛋白偶联受体介导 的信号传导机制。本研究存在局限性,包括单一性别、统一年龄组、仅限于大脑中动脉的特定中风模型以及仅预定一个缺血再灌注期。在未来的研究中,解决这些局限性可能会使针对中风高危个体的预防措施得以实施。

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