From the Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
Department of Anesthesiology, The University of Texas Health Science Center, McGovern Medical School, Houston, Texas.
Anesth Analg. 2020 Nov;131(5):1471-1484. doi: 10.1213/ANE.0000000000005146.
Acute respiratory distress syndrome (ARDS) is a significant cause of morbidity and mortality in the intensive care unit (ICU) and is characterized by lung epithelial and endothelial cell injury, with increased permeability of the alveolar-capillary membrane, leading to pulmonary edema, severe hypoxia, and difficulty with ventilation. The most common cause of ARDS is sepsis, and currently, treatment of ARDS and sepsis has consisted mostly of supportive care because targeted therapies have largely been unsuccessful. The molecular mechanisms behind ARDS remain elusive. Recently, a number of microRNAs (miRNAs) identified through high-throughput screening studies in ARDS patients and preclinical animal models have suggested a role for miRNA in the pathophysiology of ARDS. miRNAs are small noncoding RNAs ranging from 18 to 24 nucleotides that regulate gene expression via inhibition of the target mRNA translation or by targeting complementary mRNA for early degradation. Unsurprisingly, some miRNAs that are differentially expressed in ARDS overlap with those important in sepsis. In addition, circulatory miRNA may be useful as biomarkers or as targets for pharmacologic therapy. This can be revolutionary in a syndrome that has neither a measurable indicator of the disease nor a targeted therapy. While there are currently no miRNA-based therapies targeted for ARDS, therapies targeting miRNA have reached phase II clinical trials for the treatment of a wide range of diseases. Further studies may yield a unique miRNA profile pattern that serves as a biomarker or as targets for miRNA-based pharmacologic therapy. In this review, we discuss miRNAs that have been found to play a role in ARDS and sepsis, the potential mechanism of how particular miRNAs may contribute to the pathophysiology of ARDS, and strategies for pharmacologically targeting miRNA as therapy.
急性呼吸窘迫综合征（ARDS）是重症监护病房（ICU）发病率和死亡率的重要原因，其特征是肺上皮细胞和内皮细胞损伤，肺泡毛细血管膜通透性增加，导致肺水肿、严重缺氧和通气困难。ARDS 的最常见原因是败血症，目前，ARDS 和败血症的治疗主要包括支持性护理，因为靶向治疗基本上都没有成功。ARDS 的分子机制仍然难以捉摸。最近，通过 ARDS 患者和临床前动物模型的高通量筛选研究鉴定的许多 microRNA（miRNA）表明 miRNA 在 ARDS 的病理生理学中起作用。miRNA 是 18 到 24 个核苷酸大小的小非编码 RNA，通过抑制靶 mRNA 翻译或靶向互补 mRNA 进行早期降解来调节基因表达。毫不奇怪，ARDS 中差异表达的一些 miRNA 与败血症中重要的 miRNA 重叠。此外，循环 miRNA 可作为生物标志物或作为药物治疗的靶点。对于既没有疾病的可衡量指标，也没有靶向治疗的综合征来说，这可能是革命性的。虽然目前尚无针对 ARDS 的 miRNA 靶向治疗方法，但针对 miRNA 的治疗方法已进入针对多种疾病的 II 期临床试验。进一步的研究可能会产生一种独特的 miRNA 谱模式，作为 miRNA 靶向药物治疗的生物标志物或靶点。在这篇综述中，我们讨论了在 ARDS 和败血症中发现起作用的 miRNA，特定 miRNA 可能有助于 ARDS 病理生理学的潜在机制，以及药理学靶向 miRNA 作为治疗策略的方法。
