右美托咪定通过下调 lncRNA PACER 对慢性阻塞性肺疾病的治疗作用。

Therapeutic efficacy of dexmedetomidine on chronic obstructive pulmonary disease via downregulating lncRNA PACER.

机构信息

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

出版信息

Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12963-12970. doi: 10.26355/eurrev_202012_24200.

DOI:10.26355/eurrev_202012_24200

PMID:33378047

Abstract

OBJECTIVE

The aim of the study was to clarify the therapeutic mechanism of Dexmedetomidine (DEX) on the chronic obstructive pulmonary disease (COPD) and its regulatory effect on long non-coding RNA (lncRNA) PACER.

PATIENTS AND METHODS

Serum level of PACER in COPD patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic potential of PACER in COPD was assessed by plotting ROC curves. The in vivo COPD model was generated in rats by cigarette smoking exposure. Primary rat alveolar epithelial cells were isolated, purified and cultured. After overexpression of PACER in primary rat alveolar epithelial cells, proliferative and migratory abilities were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. Subsequently, we detected changes in PACER expression, viability and migratory potentials in primary rat alveolar epithelial cells harvested from control rats, and those harvested from COPD rats and induced with either DEX or not. Rescue experiments were conducted to uncover the involvement of PP2A in PACER-regulated cell phenotypes.

RESULTS

PACER was upregulated in serum of COPD patients, which was a potential biomarker for diagnosing COPD. Overexpression of PACER in primary rat alveolar epithelial cells enhanced proliferative and migratory abilities. Compared with primary rat alveolar epithelial cells harvested from control rats, proliferative and migratory abilities were stronger in those harvested from COPD rats and induced with either DEX or not. Notably, DEX induction decreased PACER expression, and proliferative and migratory abilities in primary rat alveolar epithelial cells harvested from COPD rats. Overexpression of PP2A could partially abolish the promotive effects of PACER on proliferative and migratory abilities in DEX-induced primary rat alveolar epithelial cells harvested from COPD rats.

CONCLUSIONS

PACER drives the proliferative and migratory abilities of alveolar epithelial cells through activating PP2A. Dexmedetomidine is conducive to COPD treatment by downregulating PACER.

摘要

目的

本研究旨在阐明右美托咪定（DEX）对慢性阻塞性肺疾病（COPD）的治疗机制及其对长链非编码 RNA（lncRNA）PACER 的调节作用。

患者和方法

通过实时定量聚合酶链反应（qRT-PCR）检测 COPD 患者血清中 PACER 的水平。通过绘制 ROC 曲线评估 PACER 在 COPD 中的诊断潜力。通过香烟暴露在大鼠中建立体内 COPD 模型。分离、纯化和培养原代大鼠肺泡上皮细胞。在原代大鼠肺泡上皮细胞中转染 PACER 后，通过细胞计数试剂盒-8（CCK-8）和 Transwell 测定分别评估细胞增殖和迁移能力。随后，我们检测了来自对照大鼠、COPD 大鼠和诱导 DEX 或不诱导 DEX 的大鼠的原代大鼠肺泡上皮细胞中 PACER 表达、活力和迁移潜能的变化。进行了挽救实验以揭示 PP2A 在 PACER 调节的细胞表型中的作用。

结果

PACER 在 COPD 患者的血清中上调，这是诊断 COPD 的潜在生物标志物。在原代大鼠肺泡上皮细胞中转染 PACER 增强了细胞的增殖和迁移能力。与来自对照大鼠的原代大鼠肺泡上皮细胞相比，来自 COPD 大鼠和诱导 DEX 或不诱导 DEX 的大鼠的原代大鼠肺泡上皮细胞的增殖和迁移能力更强。值得注意的是，DEX 诱导降低了 COPD 大鼠来源的原代大鼠肺泡上皮细胞中 PACER 的表达以及增殖和迁移能力。过表达 PP2A 可部分消除 PACER 在 COPD 大鼠来源的 DEX 诱导的原代大鼠肺泡上皮细胞中对增殖和迁移能力的促进作用。