Pulmonary pharmacology & therapeutics最新文献

Effectiveness of Mepolizumab and Dupilumab in patients with asthma-COPD overlap (ACO) compared to severe uncontrolled asthma (SUA): A retrospective observational cohort study Mepolizumab和Dupilumab在哮喘- copd重叠（ACO）患者中与严重未控制哮喘患者相比的有效性：一项回顾性观察队列研究

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2026-01-08 DOI: 10.1016/j.pupt.2025.102407

Belén Muñoz-Sánchez, Antonio León-Lloreda, David Carlos Echavarría, María Polonio-González, Juan Francisco Medina-Gallardo, Marta Ferrer-Galván, Auxiliadora Romero-Falcón, Javier Díez-Sierra, Francisco Javier Álvarez-Gutiérrez

Background

The coexistence of asthma and chronic obstructive pulmonary disease (COPD), known as asthma-COPD overlap (ACO), presents unique diagnostic and therapeutic challenges. Although biological therapies such as Mepolizumab and Dupilumab have transformed the management of severe eosinophilic asthma, their role in ACO remains poorly defined due to the exclusion of this phenotype from most clinical trials.

Methods

This retrospective observational study aimed to evaluate the real-world effectiveness of Mepolizumab and Dupilumab in patients with ACO compared to those with severe uncontrolled asthma (SUA). We included 212 patients treated in a specialized asthma unit between 2017 and 2024, all with at least 12 months of follow-up. Treatment response was assessed using clinical tools (EXACTO scale and SEPAR-REMAS criteria).

Results

Among Mepolizumab-treated patients (ACO n = 10; SUA n = 132), those with ACO had significantly lower baseline FEV₁ and lower rates of good/complete response (14.2 % vs. 60 %, p < 0.03) and clinical remission (0 % vs. 20.9 %). In the Dupilumab group (ACO n = 10; SUA n = 60), ACO patients showed lower baseline ACT scores and FEV₁, with reduced response rates (25 % vs. 55 %) and no clinical remission, although differences were not statistically significant. Despite limited power due to small ACO sample sizes, the magnitude of these differences suggests a clinically relevant reduction in biologic effectiveness in ACO.

Conclusion

These findings emphasize the urgent need for dedicated studies in ACO, a population with a high disease burden and limited treatment guidance. Individualized therapeutic approaches should be prioritized until robust clinical trial data becomes available.

背景：哮喘和慢性阻塞性肺疾病（COPD）的共存，被称为哮喘-COPD重叠（ACO），提出了独特的诊断和治疗挑战。尽管Mepolizumab和Dupilumab等生物疗法已经改变了严重嗜酸性粒细胞哮喘的治疗，但由于大多数临床试验排除了这种表型，它们在ACO中的作用仍然不明确。方法：这项回顾性观察性研究旨在评估Mepolizumab和Dupilumab在ACO患者与严重未控制哮喘（SUA）患者中的实际疗效。我们纳入了2017年至2024年间在专门哮喘病房接受治疗的212例患者，所有患者均进行了至少12个月的随访。使用临床工具（EXACTO量表和spe - remas标准）评估治疗效果。结果：在mepolizumab治疗的患者（ACO n = 10; SUA n = 132）中，ACO患者的基线FEV1显著降低，良好/完全缓解率（14.2% vs. 60%, p < 0.03）和临床缓解率（0% vs. 20.9%）较低。在Dupilumab组（ACO n = 10; SUA n = 60）， ACO患者表现出较低的基线ACT评分和FEV1，反应率降低（25% vs 55%），无临床缓解，尽管差异无统计学意义。尽管由于ACO样本量小，研究结果有限，但这些差异的大小表明ACO的生物学有效性在临床上有一定的降低。结论：这些发现强调了迫切需要对ACO进行专门研究，这是一个疾病负担高且治疗指导有限的人群。在获得可靠的临床试验数据之前，应优先考虑个体化治疗方法。

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引用次数: 0

Setting expectations with oral selexipag: an expert consensus-based approach on best practices to initiate, dose, titrate, and manage side effects (SEs) in patients with pulmonary arterial hypertension (PAH) 设定口服selexipag的期望：基于专家共识的最佳实践方法，以启动，剂量，滴定和管理肺动脉高压（PAH）患者的副作用（SEs）。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2026-01-08 DOI: 10.1016/j.pupt.2025.102406

Sheryl E. Wu , Jeremy A. Mazurek , Jennalyn D. Mayeux , Naomi G. Habib , Gurinderpal S. Doad , Christina K. Benninger , Michelle C. Cho , Paul M. Strachan , Richard M. Perry , Daisy Bridge , Medi A. Stone , Charlotte W. Oswald , Luis Val-Maranes , J. Wesley McConnell

Background

Oral selexipag, a prostacyclin receptor agonist, has been shown to delay pulmonary arterial hypertension (PAH) progression and reduce the risk of hospitalization for PAH. To ensure optimal patient outcomes with selexipag, careful treatment titration and expected side effect (SE) management are required. This study aimed to obtain expert consensus on the appropriate management of patients with PAH treated with selexipag.

Methods

United States (US) healthcare professionals (N = 17, 11 physicians; 5 nurse practitioners; 1 registered nurse) participated in this modified-Delphi panel comprising two online surveys and a consensus meeting. Consensus was defined as ≥80% panelists agreeing using a 9-point Likert scale.

Results

Panelists prescribed selexipag according to FDA label recommendations to patients with PAH. Panelists acknowledged considerations prompting adjustment in titration speed, agreeing that individual maximum dose is based on SE tolerability.

It was agreed that the duration of SEs is variable and patient-specific, however, SEs often become manageable over time. Panelists identified methods for managing SEs, agreeing this should be proactive. Panelists highlighted the importance of communicating with patients to set expectations, to enhance engagement and adherence.

Panelists agreed that treatment initiation, titration, and SE management should be individualized to suit each patient, with decision-making primarily based on patient characteristics and treatment preference.

Discussion

This panel provided expert opinions on the clinical use of and best practices for treatment titration and management of expected SEs for oral selexipag. Insights are valuable for developing standardized clinical guidelines and best practices, as well as ensuring personalized treatment to improve patient care.

背景：口服selexipag是一种前列环素受体激动剂，已被证明可以延缓肺动脉高压（PAH）的进展并降低PAH住院的风险。为了确保患者使用selexipag的最佳结果，需要仔细的治疗滴定和预期的副作用（SE）管理。本研究旨在就selexipag治疗PAH患者的适当管理获得专家共识。方法：美国医疗保健专业人员（N=17, 11名内科医生，5名执业护士，1名注册护士）参与了这个修改的德尔菲小组，包括两次在线调查和一次共识会议。共识被定义为≥80%的小组成员同意使用9分李克特量表。结果：小组成员根据FDA标签对PAH患者的推荐处方selexipag。小组成员承认需要考虑调整滴定速度，同意个人最大剂量是基于硒耐受性。人们一致认为，SEs的持续时间是可变的，因人而异，然而，随着时间的推移，SEs通常变得可控。小组成员确定了管理企业的方法，并同意这应该是积极主动的。小组成员强调了与患者沟通的重要性，以设定期望，提高参与度和依从性。小组成员一致认为，治疗开始、滴定和SE管理应个体化，以适应每位患者，决策主要基于患者特征和治疗偏好。讨论：该小组就口服selexipag的临床使用和治疗滴定的最佳实践以及预期SEs的管理提供了专家意见。这些见解对于制定标准化的临床指南和最佳实践，以及确保个性化治疗以改善患者护理非常有价值。

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引用次数: 0

Artificial intelligence in the development of Rentosertib: A novel TNIK inhibitor for idiopathic pulmonary fibrosis – A letter to editor 人工智能在Rentosertib开发中的应用：一种治疗特发性肺纤维化的新型TNIK抑制剂-致编辑的一封信

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-12-30 DOI: 10.1016/j.pupt.2025.102405

Devipriya R. Namboothiri , Aswathy Sivanandan , Gladyston Netto , Midhun Mathew

引用次数: 0

Advances in novel therapeutics for idiopathic pulmonary fibrosis 特发性肺纤维化新疗法研究进展。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-10-20 DOI: 10.1016/j.pupt.2025.102396

Menghao Li , Bokun Chen , Xinhui Zhang, Tingting Zhuo, Xiuju Liu

IPF is a chronic, progressive interstitial lung disease characterized by irreversible lung scarring, leading to exertional dyspnea and a gradual decline in pulmonary function. Its pathogenesis involves multiple mechanisms, including chronic inflammation, aberrant cytokine signaling, and alveolar epithelial injury. Currently, IPF remains incurable, and treatment primarily aims to slow disease progression and improve survival. This paper systematically reviews recent clinical trials of novel IPF drug therapies that have demonstrated promising efficacy, aiming to inform future drug development.

IPF是一种慢性进行性间质性肺疾病，其特征是不可逆的肺瘢痕形成，导致用力呼吸困难和肺功能逐渐下降。其发病机制涉及多种机制，包括慢性炎症、细胞因子信号异常和肺泡上皮损伤。目前，IPF仍然无法治愈，治疗的主要目的是减缓疾病进展和提高生存率。本文系统回顾了近年来新型IPF药物治疗的临床试验，这些试验已经证明了有希望的疗效，旨在为未来的药物开发提供信息。

引用次数: 0

Drug-drug interactions in vanzacaftor–tezacaftor–deutivacaftor versus elexacaftor–tezacaftor-ivacaftor vanzacator - tezacator - detivacator与elexaftor - tezacator - ivacaftor的药物相互作用。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-10-18 DOI: 10.1016/j.pupt.2025.102395

Esen Deniz Akman Ar, Nadir Yalcin

引用次数: 0

Targeting the immunometabolism interface: A novel strategy for IPF therapy 靶向免疫代谢界面：IPF治疗的新策略

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-09-10 DOI: 10.1016/j.pupt.2025.102394

Ganggang Li , Yuzhi Huo , Xiaochuan Pan , Nan Jia , Xuanyu Wu , Xinhui Wu , Fei Wang , Quanyu Du

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by aberrant tissue remodeling and excessive deposition of extracellular matrix components. Emerging evidence underscores the critical role of the immunometabolism in the pathogenesis of IPF, highlighting how dysregulated metabolic pathways modulate immune responses and contribute to fibrotic progression. Key molecular regulators such as PPARG (peroxisome proliferator activated receptor gamma) and SPP1 (secreted phosphoprotein 1), along with signaling pathways including mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and hypoxia-inducible factor 1-alpha (HIF-1α), orchestrate immune cell polarization, fibroblast activation, and extracellular matrix production. These insights reveal promising therapeutic targets at the intersection of metabolism and immunity. This review synthesizes current findings on immunometabolism interactions in IPF, emphasizing the potential of metabolic reprogramming and immune modulation as novel treatment strategies. Despite substantial advances, significant challenges persist in elucidating the precise mechanisms underlying these interactions and translating preclinical insights into effective clinical interventions. Future research should prioritize the identification of actionable metabolic biomarkers, refinement of molecular targets, and development of personalized therapeutic approaches. Addressing these gaps may pave the way for innovative therapies capable of halting or even reversing fibrosis, ultimately improving outcomes for patients with IPF.

特发性肺纤维化（IPF）是一种慢性进行性间质性肺疾病，其特征是异常组织重塑和细胞外基质成分过度沉积。新出现的证据强调了免疫代谢在IPF发病机制中的关键作用，强调了失调的代谢途径如何调节免疫反应并促进纤维化进展。关键的分子调节因子，如PPARG（过氧化物酶体增殖体激活受体γ）和SPP1（分泌磷酸化蛋白1），以及包括哺乳动物雷帕霉素靶点（mTOR）、amp激活蛋白激酶（AMPK）和缺氧诱导因子1- α (HIF-1α)在内的信号通路，协调免疫细胞极化、成纤维细胞激活和细胞外基质的产生。这些见解揭示了代谢和免疫交叉的有希望的治疗靶点。本文综述了IPF中免疫代谢相互作用的最新研究结果，强调了代谢重编程和免疫调节作为新的治疗策略的潜力。尽管取得了重大进展，但在阐明这些相互作用的确切机制以及将临床前见解转化为有效的临床干预措施方面，仍然存在重大挑战。未来的研究应优先确定可操作的代谢生物标志物，改进分子靶点，并开发个性化的治疗方法。解决这些空白可能为能够阻止甚至逆转纤维化的创新疗法铺平道路，最终改善IPF患者的预后。

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引用次数: 0

Exploring the role of β2- and β3-adrenergic receptors in cystic fibrosis 探讨β2-和β3肾上腺素能受体在囊性纤维化中的作用

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-08-18 DOI: 10.1016/j.pupt.2025.102385

Alessandro Cannavo , Marika Comegna , Alice Castaldo , Caterina Vinciguerra , Anna Lauritano , Giulia Renata Franco , Giovanna Casoria , Graziamaria Corbi , Giuseppe Rengo , Giuseppe Castaldo

Cystic fibrosis (CF) is an autosomal recessive disorder that affects multiple organs, with clinical manifestations, disease progression, and response to therapy varying among individuals. This effect is mainly caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel.

In recent decades, other genes and their allelic variants, beyond CFTR mutations, have been proposed as genetic modifiers of CF phenotype. For instance, different polymorphic β2-adrenergic receptor (β2AR) polymorphic variants have been reported in CF individuals and appear to influence correct receptor function. β2AR belongs to the βAR family, which includes three subtypes: β1AR, β2AR, and β3AR. These receptors are crucial G protein-coupled receptors (GPCRs) expressed in various cell types and serve as key modulators of cAMP production, making their function particularly relevant in CF pathophysiology. β2AR is abundantly expressed in airway epithelial and smooth muscle cells, and studies revealed that it plays a crucial role in modulating CFTR activity and smooth muscle contractility through cAMP signaling. For these reasons, β2-agonists are widely used in clinical healthcare to treat patients with obstructive airway disorders, including CF.

Emerging evidence has also supported a role for β3AR, which is expressed in the canine and human bronchial epithelium and have been reported to enhance ciliary motility and regulate CFTR function, making it a potential therapeutic target in CF.

囊性纤维化（CF）是一种常染色体隐性遗传病，可影响多个器官，其临床表现、疾病进展和对治疗的反应因人而异。这种影响主要是由编码CF跨膜电导调节器（CFTR）的基因突变引起的，CFTR是camp调节的氯离子通道。近几十年来，除了CFTR突变外，其他基因及其等位变异也被认为是CF表型的遗传修饰因子。例如，在CF个体中已经报道了不同的多态β2-肾上腺素能受体（β2AR）多态变异，并且似乎影响了正确的受体功能。β2AR属于βAR家族，包括β1AR、β2AR和β3AR三个亚型。这些受体是关键的G蛋白偶联受体（gpcr），在各种细胞类型中表达，并作为cAMP产生的关键调节剂，使其功能与CF病理生理特别相关。β2AR在气道上皮细胞和平滑肌细胞中大量表达，研究发现它通过cAMP信号通路在调节CFTR活性和平滑肌收缩力中起着至关重要的作用。由于这些原因，β2激动剂被广泛应用于临床医疗保健，用于治疗包括CF在内的阻塞性气道疾病。新的证据也支持β3AR的作用，β3AR在犬和人的支气管上皮中表达，据报道可增强纤毛运动性并调节CFTR功能，使其成为CF的潜在治疗靶点。

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引用次数: 0

FTO regulates the proliferation and apoptosis of pulmonary artery smooth muscle cells through m6A demethylation modification FTO通过m6A去甲基化修饰调控肺动脉平滑肌细胞的增殖和凋亡。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-08-14 DOI: 10.1016/j.pupt.2025.102382

Xinwei Shi , Yizhou Yang , Yue Gao , Chao Yuan , Xianqun Rao , Wei Li , Liting Wu , Tingting Yu , Ming Xu , Baoli Zhu , Lei Han , Kai Sun

Background

To investigate whether FTO-mediated N6-methyladenosine (m6A) demethylation affects the proliferative/apoptotic phenotype of mouse pulmonary artery smooth muscle cells (PASMCs).

Methods

The hypoxia model of PASMCs was established to examine changes in FTO protein expression and m6A modification levels. Cell transfection, m6A expression profiling, mRNA stability testing, and protein-RNA binding assays were used to explore the effects of FTO and its downstream target, CACNA1d, on PASMC proliferation and apoptosis.

Results

Hypoxia downregulated FTO expression and upregulated m6A modification, leading to enhanced proliferation and reduced apoptosis in PASMCs. Overexpression of FTO reversed these effects, while FTO knockdown under normoxia mimicked the hypoxia-induced "pro-proliferative and anti-apoptotic" changes. Genome-wide m6A profiling identified CACNA1d as a potential downstream target of FTO, with YTHDC1 acting as the m6A reader. FTO binds CACNA1d mRNA and reduces its stability via m6A demethylation. CACNA1d knockdown partially mitigated the hypoxia-induced changes in PASMC proliferation and apoptosis. In addition, when the hypoxic culture was returned to normoxic culture, the level of apoptosis in PASMCs was restored to the pre-hypoxic level, and this was still observed after the overexpression of FTO or knockdown of CACNA1d expression.

Conclusion

FTO downregulation in hypoxic PASMCs increases m6A modification, promoting proliferation and inhibiting apoptosis by enhancing CACNA1d expression.

背景：研究fto介导的n6 -甲基腺苷（m6A）去甲基化是否影响小鼠肺动脉平滑肌细胞（PASMCs）的增殖/凋亡表型。方法：建立PASMCs缺氧模型，检测FTO蛋白表达及m6A修饰水平的变化。通过细胞转染、m6A表达谱、mRNA稳定性测试和蛋白- rna结合实验，探讨FTO及其下游靶点CACNA1d对PASMC增殖和凋亡的影响。结果：缺氧可下调PASMCs FTO表达，上调m6A修饰，导致PASMCs增殖增强，凋亡减少。FTO的过表达逆转了这些作用，而在常氧条件下FTO的敲低模拟了缺氧诱导的“促增殖和抗凋亡”的变化。全基因组m6A分析鉴定了CACNA1d作为FTO的潜在下游靶点，YTHDC1作为m6A读取器。FTO结合CACNA1d mRNA并通过m6A去甲基化降低其稳定性。CACNA1d敲低可部分减轻缺氧诱导的PASMC增殖和凋亡的变化。此外，当缺氧培养恢复到常氧培养时，PASMCs的凋亡水平恢复到缺氧前水平，并且在过表达FTO或敲低CACNA1d表达后仍能观察到这种情况。结论：缺氧PASMCs中FTO下调可增加m6A修饰，通过提高CACNA1d表达促进细胞增殖，抑制细胞凋亡。

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引用次数: 0

Pharmacovigilance of five commonly used antibiotics in acute exacerbations of COPD (AECOPD): Analysis of the FDA adverse event reporting system database 慢性阻塞性肺病急性加重期（AECOPD） 5种常用抗生素的药物警戒：FDA不良事件报告系统数据库分析

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-08-11 DOI: 10.1016/j.pupt.2025.102383

Qin Shen , Suzhen Yang , Sha Wang

Objective

Antibiotics are commonly administered during acute exacerbations of chronic obstructive pulmonary disease (AECOPD) to manage infections and alleviate their symptoms. However, their use may result in adverse drug events (ADEs), potentially compromising patient safety and treatment effectiveness. The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) provides valuable data for identifying such risks. This study aimed to analyze FAERS data to detect ADE signals associated with antibiotic use in patients with AECOPD, thereby supporting safer clinical practices.

Methods

Five antibiotics frequently used in AECOPD management, azithromycin, moxifloxacin, meropenem, gentamicin, and minocycline, were selected for analysis. FAERS data from January 1, 2004, to July 30, 2024, were extracted using OpenVigil 2.1 platform. Duplicate and incomplete reports were excluded. ADEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA). Data mining techniques, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used to identify statistically significant ADE signals.

Results

111,179 ADE reports involving 100,602 patients were identified, including azithromycin (41,241 reports), moxifloxacin (46,770), meropenem (5,904), gentamicin (4,142), and minocycline (13,122). Serious events comprised 30.6 %–47.1 % of the reported ADEs, with the lowest proportion observed for meropenem, and the highest proportion observed for gentamicin. Females accounted for 57.0 % of the cases with known gender. Data mining identified 1946 ADE signals, including novel associations such as infectious chondromatosis (azithromycin), hemorrhagic obstructive retinal vasculitis (moxifloxacin), elevated procalcitonin (meropenem), Bartter syndrome (gentamicin), and nodular polyarteritis (minocycline).

Conclusion

This study identified novel ADE signals associated with antibiotics used in AECOPD treatment, highlighting the importance of continuous pharmacovigilance. Clinicians should be informed of the emerging safety concerns to enhance patient care.

目的慢性阻塞性肺疾病（AECOPD）急性加重期通常使用抗生素来控制感染并减轻其症状。然而，它们的使用可能导致药物不良事件（ADEs），潜在地损害患者安全和治疗效果。美国食品和药物管理局不良事件报告系统（FAERS）为识别此类风险提供了有价值的数据。本研究旨在分析FAERS数据，以检测与AECOPD患者抗生素使用相关的ADE信号，从而支持更安全的临床实践。方法选取阿奇霉素、莫西沙星、美罗培南、庆大霉素、米诺环素5种AECOPD常用抗生素进行分析。2004年1月1日至2024年7月30日FAERS数据采用OpenVigil 2.1平台提取。排除了重复和不完整的报告。使用药物调节活动医学词典（MedDRA）对ade进行编码。数据挖掘技术，包括比例报告比（PRR）和报告优势比（ROR），用于识别具有统计学意义的ADE信号。结果共发现111,179例ADE报告，涉及100,602例患者，包括阿奇霉素（41,241例）、莫西沙星（46,770例）、美罗培南（5,904例）、庆大霉素（4,142例）和米诺环素（13,122例）。严重事件发生率为30.6% ~ 47.1%，其中美罗培南发生率最低，庆大霉素发生率最高。已知性别的病例中，女性占57.0%。数据挖掘确定了1946年ADE信号，包括新的关联，如感染性软骨瘤病（阿奇霉素）、出血性阻塞性视网膜血管炎（莫西沙星）、降钙素原升高（美罗培南）、巴氏综合征（庆大霉素）和结节性多动脉炎（米诺环素）。结论本研究发现了与AECOPD治疗中使用的抗生素相关的新型ADE信号，强调了持续药物警戒的重要性。临床医生应了解新出现的安全问题，以加强对患者的护理。

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引用次数: 0

Functional interplay between bradykinin receptors and transient receptor potential vanilloid-1 in lipopolysaccharide-induced acute lung injury in mice 缓激肽受体与瞬时受体电位香草素-1在脂多糖诱导的小鼠急性肺损伤中的功能相互作用

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-08-10 DOI: 10.1016/j.pupt.2025.102384

Mayara Alves Amorim , Vitor Hélio Souza Oliveira , João B. Calixto , Eunice André

In this study, we investigated the functional interplay between bradykinin receptors and the transient receptor potential vanilloid-1 (TRPV1) channel in a mouse model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Lung and bronchoalveolar lavages were collected at 6 and 24 h after the induction of ALI and evaluated for changes in body weight, inflammatory marker levels, lung injury, and TRPV1 expression. Pretreatments with a TRPV1 antagonist (capsazepine) or B₁ and B₂ receptor antagonists, i.e., DALBK and HOE 140, respectively, were evaluated in this ALI mouse model. The histological score revealed higher levels of lung injury in mice treated with LPS (5 and 10 mg/kg), assessed at both 6 and 24 h, compared to the vehicle-treated group. A loss of body weight was observed within 24 h of ALI induction. Furthermore, collagen deposition, pulmonary oedema, leukocyte influx, and increased cytokine levels were also observed following LPS administration. Pretreatment with capsazepine, DALBK, or HOE 140 not only reversed all inflammatory parameters but also prevented the increased expression of TRPV1 observed in the lungs of mice subjected LPS-induced ALI. Our data suggest that, following LPS-induced ALI, bradykinin activates both B₁ and B₂ receptors associated with the subsequent activation of TRPV1. These findings suggest that bradykinin can activate both B₁ and B₂ receptors, which may contribute functionally to TRPV1 upregulation and activation during LPS-induced ALI. This novel pathway appears to sustain inflammation, offering a new therapeutic target for ALI and ARDS.

在本研究中，我们研究了缓激肽受体与瞬时受体电位香草素-1 （TRPV1）通道在脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠模型中的功能相互作用。在ALI诱导后6和24小时收集肺和支气管肺泡灌洗液，评估体重、炎症标志物水平、肺损伤和TRPV1表达的变化。用TRPV1拮抗剂（辣椒平）或B1和B2受体拮抗剂（分别为DALBK和ho140）预处理ALI小鼠模型进行评估。组织学评分显示，LPS（5和10 mg/kg）处理的小鼠在6和24小时的肺损伤水平均高于给药组。在ALI诱导24小时内观察到体重下降。此外，胶原沉积、肺水肿、白细胞内流和细胞因子水平升高也在LPS处理后被观察到。用辣椒平、DALBK或ho140预处理不仅可以逆转所有炎症参数，还可以阻止lps诱导的ALI小鼠肺中TRPV1表达的增加。我们的数据表明，在lps诱导的ALI后，缓激肽激活了与随后激活TRPV1相关的B1和B2受体。这些发现表明，缓激素可以激活B1和B2受体，这可能在功能上有助于lps诱导的ALI中TRPV1的上调和激活。这种新途径似乎可以维持炎症，为ALI和ARDS提供新的治疗靶点。

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引用次数: 0