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运动诱导的下肢缺血导致外周动脉疾病患者的线粒体复合物 I 缺陷。

Mitochondrial complex I defect resulting from exercise-induced lower limb ischemia in patients with peripheral arterial disease.

机构信息

Laboratory for Vascular Investigation, University Hospital , Angers , France.

Department of Biochemistry and Genetics, University Hospital , Angers , France.

出版信息

J Appl Physiol (1985). 2018 Sep 1;125(3):938-946. doi: 10.1152/japplphysiol.00059.2018. Epub 2018 May 24.

DOI:10.1152/japplphysiol.00059.2018
PMID:29792553
Abstract

This study aims to compare the structural and mitochondrial alterations between muscle segments affected by exercise-induced ischemia and segments of the same muscle without ischemia, in the same subject. In a prospective analysis, 34 patients presenting either peripheral arterial disease or chronic coronary syndrome without any evidence of peripheral arterial disease were eligible for inclusion based on findings indicating a need for either a femoro-popliteal bypass or a saphenous harvesting for coronary bypass. Before surgery, we assessed the level of exercise-induced ischemia in proximal and distal sections of the thigh by the measurement of transcutaneous oxygen pressure during an exercise treadmill test. Distal and proximal biopsies of the sartorius muscle were procured during vascular surgical procedures to assess mitochondrial function and morphometric parameters of the sartorius myofibers. Comparisons were made between the distal and proximal biopsies, with respect to these parameters. Thirteen of the study patients that initially presented with peripheral arterial disease had evidence of an isolated distal thigh exercise-induced ischemia, associated with a 35% decrease in the mitochondrial complex I enzymatic activity in the distal muscle biopsy. This defect was also associated with a decreased expression of the manganese superoxide dismutase enzyme and with alterations of the shapes of the myofibers. No functional or structural alterations were observed in the patients with coronary syndrome. We validated a specific model ischemia in peripheral arterial disease characterized by muscular alterations. This "Distal-Proximal-Sartorius Model" would be promising to explore the physiopathological consequences specific to chronic ischemia. NEW & NOTEWORTHY We compared proximal versus distal biopsies of the sartorius muscle in patients with superficial femoral artery stenosis or occlusion and proof of, distal only, regional blood flow impairment with exercise oximetry. We identified a decrease in the mitochondrial complex I enzymatic activity and antioxidant system impairment at the distal level only. We validate a model to explore the physiopathological consequences of chronic muscle ischemia.

摘要

这项研究旨在比较同一受试者中受运动诱导缺血影响的肌肉段与同一肌肉中无缺血的肌肉段之间的结构和线粒体变化。在一项前瞻性分析中,根据需要进行股-腘旁路或隐静脉采集用于冠状动脉旁路的发现,纳入了 34 名患有周围动脉疾病或慢性冠状动脉综合征但无周围动脉疾病证据的患者。在手术前,我们通过在跑步机运动试验期间测量经皮氧分压来评估大腿近端和远端的运动诱导缺血程度。在血管外科手术过程中采集股薄肌的远端和近端活检,以评估股薄肌纤维的线粒体功能和形态学参数。比较这些参数在远端和近端活检之间的差异。最初患有周围动脉疾病的 13 名研究患者有孤立的大腿远端运动诱导缺血的证据,与远端肌肉活检中线粒体复合物 I 酶活性降低 35%相关。这种缺陷还与锰超氧化物歧化酶酶表达降低和肌纤维形状改变有关。在患有冠状动脉综合征的患者中未观察到功能或结构改变。我们验证了一种特定的外周动脉疾病模型缺血,其特征为肌肉改变。这种“远端-近端-股薄肌模型”将有望探索慢性缺血特有的生理病理后果。新内容和值得注意的内容我们比较了股薄肌近端和远端活检在股浅动脉狭窄或闭塞以及运动血氧测定证明只有远端区域血流受损的患者中的差异。我们仅在远端发现线粒体复合物 I 酶活性和抗氧化系统损伤降低。我们验证了一种模型来探索慢性肌肉缺血的生理病理后果。

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