{"title":"伊塔康酸治疗急性肺损伤:临床前模型的最新进展和启示。","authors":"Qin Juan Wu, Qian Li, Ping Yang, Lei Du","doi":"10.62347/NUIN2087","DOIUrl":null,"url":null,"abstract":"<p><p>Acute lung injury (ALI) is defined as the acute onset of diffuse bilateral pulmonary infiltration, leading to PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 300 mmHg without clinical evidence of left atrial hypertension. Acute respiratory distress syndrome (ARDS) involves more severe hypoxemia (PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 200 mmHg). Treatment of ALI and ARDS has received renewed attention as the incidence of ALI caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has increased. Itaconate and its derivatives have shown therapeutic potential against ALI. This review provides an in-depth summary of the mechanistic research of itaconate in the field of acute lung injury, including inducing autophagy, preventing ferroptosis and pyroptosis, shifting macrophage polarization to an anti-inflammatory M2 phenotype, inhibiting neutrophil activation, regulating epigenetic modifications, and repressing aerobic glycolysis. These compounds merit further consideration in clinical trials. We anticipate that the clinical translation of itaconate-based drugs can be accelerated.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384376/pdf/","citationCount":"0","resultStr":"{\"title\":\"Itaconate to treat acute lung injury: recent advances and insights from preclinical models.\",\"authors\":\"Qin Juan Wu, Qian Li, Ping Yang, Lei Du\",\"doi\":\"10.62347/NUIN2087\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Acute lung injury (ALI) is defined as the acute onset of diffuse bilateral pulmonary infiltration, leading to PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 300 mmHg without clinical evidence of left atrial hypertension. Acute respiratory distress syndrome (ARDS) involves more severe hypoxemia (PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 200 mmHg). Treatment of ALI and ARDS has received renewed attention as the incidence of ALI caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has increased. Itaconate and its derivatives have shown therapeutic potential against ALI. This review provides an in-depth summary of the mechanistic research of itaconate in the field of acute lung injury, including inducing autophagy, preventing ferroptosis and pyroptosis, shifting macrophage polarization to an anti-inflammatory M2 phenotype, inhibiting neutrophil activation, regulating epigenetic modifications, and repressing aerobic glycolysis. These compounds merit further consideration in clinical trials. We anticipate that the clinical translation of itaconate-based drugs can be accelerated.</p>\",\"PeriodicalId\":7731,\"journal\":{\"name\":\"American journal of translational research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384376/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of translational research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.62347/NUIN2087\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of translational research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/NUIN2087","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
急性肺损伤(ALI)是指急性发作的弥漫性双侧肺浸润,导致 PaO2/FiO2 ≤ 300 mmHg,但无左心房高压的临床证据。急性呼吸窘迫综合征(ARDS)涉及更严重的低氧血症(PaO2/FiO2 ≤ 200 mmHg)。随着严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)感染引起的 ALI 发病率的增加,ALI 和 ARDS 的治疗再次受到关注。伊塔康酸及其衍生物已显示出对 ALI 的治疗潜力。本综述深入总结了伊塔康酸在急性肺损伤领域的机理研究,包括诱导自噬、防止铁变态反应和热变态反应、将巨噬细胞极化转变为抗炎 M2 表型、抑制中性粒细胞活化、调节表观遗传修饰和抑制有氧糖酵解。这些化合物值得在临床试验中进一步考虑。我们预计,伊它康酸类药物的临床转化可以加速。
Itaconate to treat acute lung injury: recent advances and insights from preclinical models.
Acute lung injury (ALI) is defined as the acute onset of diffuse bilateral pulmonary infiltration, leading to PaO2/FiO2 ≤ 300 mmHg without clinical evidence of left atrial hypertension. Acute respiratory distress syndrome (ARDS) involves more severe hypoxemia (PaO2/FiO2 ≤ 200 mmHg). Treatment of ALI and ARDS has received renewed attention as the incidence of ALI caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has increased. Itaconate and its derivatives have shown therapeutic potential against ALI. This review provides an in-depth summary of the mechanistic research of itaconate in the field of acute lung injury, including inducing autophagy, preventing ferroptosis and pyroptosis, shifting macrophage polarization to an anti-inflammatory M2 phenotype, inhibiting neutrophil activation, regulating epigenetic modifications, and repressing aerobic glycolysis. These compounds merit further consideration in clinical trials. We anticipate that the clinical translation of itaconate-based drugs can be accelerated.