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骨髓干细胞疗法可缓解慢性阻塞性肺疾病-阻塞性睡眠呼吸暂停重叠综合征大鼠模型中的血管损伤。

Bone marrow stem cells therapy alleviates vascular injury in a chronic obstructive pulmonary disease‑obstructive sleep apnea overlap syndrome rat model.

机构信息

Department of Pneumology, The First People's Hospital‑Calmette Hospital of Kunming, Kunming, Yunnan 650224, P.R. China.

出版信息

Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11707. Epub 2020 Nov 25.

DOI:10.3892/mmr.2020.11707
PMID:33236768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7716420/
Abstract

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are highly prevalent potential risk factors for systemic disease. Previous studies have reported that COPD and OSA are major independent risk factors for cardio‑ or cerebrovascular diseases. The present study aimed to investigate the role of bone marrow mesenchymal stem cells (BMSCs) on vascular injury in a COPD‑OSA overlap syndrome (OS) rat model. Rats were randomly divided into three groups: Sham, OS model and BMSC. BMSC localization in major organs was detected via confocal laser fluorescence microscopy, and the aortic tissue pathological changes and related genes were measured using hematoxylin & eosin and Masson staining. Genes associated with vascular endothelial cell injury, including endothelin 1, vascular cell adhesion molecule 1 and endothelial nitric oxide synthase, were detected via reverse transcription‑quantitative PCR and western blotting. Apoptosis of vascular endothelial cells was detected using TUNEL and immunofluorescence assays. The endothelial cell marker CD31 in injured vessels was analyzed via immunohistochemistry. BMSCs migrated into the heart, liver, spleen, lung, kidney, brain and aorta in the OS model. The green fluorescence expression of BMSCs demonstrated the highest level in the lung, followed by the aorta. Aortic tissue had a more severe vascular injury and increased apoptosis in the model group compared with the BMSC group. Vascular endothelial cell apoptosis was decreased in the BMSC group compared with the model group. The findings suggested that BMSCs could repair vascular injury by inhibiting endothelial cell damage and apoptosis. These data provide a theoretical basis for the treatment of cardiovascular diseases caused by OS with BMSCs.

摘要

慢性阻塞性肺疾病(COPD)和阻塞性睡眠呼吸暂停(OSA)是全身性疾病的高发潜在危险因素。既往研究报道,COPD 和 OSA 是心脑血管疾病的主要独立危险因素。本研究旨在探讨骨髓间充质干细胞(BMSCs)在 COPD-OSA 重叠综合征(OS)大鼠模型血管损伤中的作用。大鼠随机分为三组:假手术组、OS 模型组和 BMSC 组。通过共聚焦激光荧光显微镜检测 BMSC 在主要器官中的定位,采用苏木精和伊红及 Masson 染色检测主动脉组织的病理变化和相关基因。通过逆转录-定量 PCR 和 Western blot 检测与血管内皮细胞损伤相关的基因,包括内皮素 1、血管细胞黏附分子 1 和内皮型一氧化氮合酶。通过 TUNEL 和免疫荧光检测血管内皮细胞凋亡。通过免疫组化分析损伤血管中的内皮细胞标志物 CD31。BMSC 迁移到 OS 模型的心脏、肝脏、脾脏、肺、肾脏、大脑和主动脉。BMSC 的绿色荧光表达在肺中最高,其次是主动脉。与 BMSC 组相比,模型组的主动脉组织血管损伤更严重,细胞凋亡增加。与模型组相比,BMSC 组血管内皮细胞凋亡减少。这些结果表明,BMSCs 可通过抑制内皮细胞损伤和凋亡来修复血管损伤。这些数据为使用 BMSCs 治疗 OS 引起的心血管疾病提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/ee6b95836352/mmr-23-01-11707-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/5e154e80134b/mmr-23-01-11707-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/8362516f1e8b/mmr-23-01-11707-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/96081f93de73/mmr-23-01-11707-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/ad465d642128/mmr-23-01-11707-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/ee6b95836352/mmr-23-01-11707-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/5e154e80134b/mmr-23-01-11707-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/8362516f1e8b/mmr-23-01-11707-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/96081f93de73/mmr-23-01-11707-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/ad465d642128/mmr-23-01-11707-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7078/7716420/ee6b95836352/mmr-23-01-11707-g04.jpg

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