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COPD 患者骨骼肌中 PPARα mRNA 表达与线粒体呼吸功能和超微结构的关系。

Relationship between PPARα mRNA expression and mitochondrial respiratory function and ultrastructure of the skeletal muscle of patients with COPD.

机构信息

a Department of Respiratory Critical Care Medicine , the First Affiliated Hospital of Kunming Medical University , Kunming , China.

b Department of hematology , the First Affiliated Hospital of Kunming Medical University , Kunming , China.

出版信息

Bioengineered. 2017 Nov 2;8(6):723-731. doi: 10.1080/21655979.2017.1346757. Epub 2017 Aug 11.

DOI:10.1080/21655979.2017.1346757
PMID:28708015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5736346/
Abstract

Peripheral muscle dysfunction is an important complication in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to explore the relationship between the levels of peroxisome proliferator-activated receptor α (PPARα) mRNA expression and the respiratory function and ultrastructure of mitochondria in the vastus lateralis of patients with COPD. Vastus lateralis biopsies were performed on 14 patients with COPD and 6 control subjects with normal lung function. PPARα mRNA levels in the muscle tissue were detected by real-time PCR. A Clark oxygen electrode was used to assess mitochondrial respiratory function. Mitochondrial number, fractional area in skeletal muscle cross-sections, and Z-line width were observed via transmission electron microscopy. The PPARα mRNA expression was significantly lower in COPD patients with low body mass index (BMIL) than in both COPD patients with normal body mass index (BMIN) and controls. Mitochondrial respiratory function (assessed by respiratory control ratio) was impaired in COPD patients, particularly in BMIL. Compared with that in the control group, mitochondrial number and fractional area were lower in the BMIL group, but were maintained in the BMIN group. Further, the Z-line became narrow in the BMIL group. PPARα mRNA expression was positively related to mitochondrial respiratory function and volume density. In COPD patients with BMIN, mitochondria volume density was maintained, while respiratory function decreased, whereas both volume density and respiratory function decreased in COPD patients with BMIL. PPARα mRNA expression levels are associated with decreased mitochondrial respiratory function and volume density, which may contribute to muscle dysfunction in COPD patients.

摘要

外周肌肉功能障碍是慢性阻塞性肺疾病(COPD)患者的重要并发症。本研究旨在探讨过氧化物酶体增殖物激活受体α(PPARα)mRNA 表达水平与 COPD 患者股外侧肌呼吸功能和线粒体超微结构的关系。对 14 例 COPD 患者和 6 例肺功能正常的对照组进行股外侧肌活检。采用实时 PCR 检测肌肉组织中 PPARα mRNA 水平。采用 Clark 氧电极评估线粒体呼吸功能。通过透射电镜观察线粒体数量、骨骼肌横切面积分数和 Z 线宽度。低体重指数(BMI)的 COPD 患者的 PPARα mRNA 表达明显低于正常 BMI 的 COPD 患者和对照组。COPD 患者的线粒体呼吸功能(通过呼吸控制比评估)受损,尤其是 BMI 较低的患者。与对照组相比,BMI 较低组的线粒体数量和面积分数较低,但在 BMI 正常组中则得以维持。此外,BMI 较低组的 Z 线变窄。PPARα mRNA 表达与线粒体呼吸功能和体积密度呈正相关。在 BMI 正常的 COPD 患者中,线粒体体积密度得以维持,而呼吸功能下降;而在 BMI 较低的 COPD 患者中,线粒体体积密度和呼吸功能均下降。PPARα mRNA 表达水平与线粒体呼吸功能和体积密度降低有关,这可能是 COPD 患者肌肉功能障碍的原因之一。

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