Sacubitril/缬沙坦作为肺纤维化的调节剂：Lnc-SNHG-16/miR-455调节和Notch/Smad-3通路抑制的见解
Sacubitril/valsartan as a modulator of pulmonary fibrosis: insights into Lnc-SNHG-16/miR-455 modulation and Notch/Smad-3 pathway inhibition.
摘要(中文译文)
肺纤维化是一种进行性且危及生命的间质性肺疾病，以细胞外基质过度积聚和肺功能下降为特征。尽管已有可用疗法，临床结局仍不理想，因此需要探索新的治疗途径。沙库巴曲/缬沙坦是一种兼具脑啡肽酶抑制剂和血管紧张素II受体拮抗剂的双重作用药物，近年来作为具有潜在抗纤维化特性的候选药物受到关注。本研究在博来霉素诱导的大鼠肺纤维化模型中探讨沙库巴曲/缬沙坦的治疗效果。该化合物自纤维化诱导第一天起每日口服一次，持续21天。通过生化和组织学评估纤维化进展，包括羟脯氨酸含量、α-平滑肌肌动蛋白（α-SMA）表达、胶原沉积百分比的定量以及肺组织病理学检查。分子分析显示，沙库巴曲/缬沙坦显著下调长链非编码RNA SNHG-16的表达，同时上调miR-455水平。这些变化与Notch-2/Smad-3信号通路的抑制相关。此外，沙库巴曲/缬沙坦治疗使肺组织中转化生长因子-β（TGF-β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平显著降低，表明纤维化和炎症反应均受到减弱。总体而言，这些发现提示沙库巴曲/缬沙坦通过调控SNHG-16/miR-455轴及抑制Notch-2/Smad-3/TGF-β信号级联来减轻肺纤维化，凸显其作为肺纤维化治疗策略的潜力。
Abstract
Pulmonary fibrosis is a progressive and life-threatening interstitial lung disease marked by excessive extracellular matrix accumulation and declining pulmonary function. Despite available therapies, clinical outcomes remain suboptimal, necessitating the exploration of novel therapeutic approaches. Sacubitril/valsartan, a dual-acting agent combining a neprilysin inhibitor and angiotensin II receptor blocker, has recently emerged as a candidate with potential anti-fibrotic properties. This study investigates the therapeutic efficacy of sacubitril/valsartan in a bleomycin-induced rat model of pulmonary fibrosis. The compound was administered orally once daily, beginning on the first day of fibrosis induction and continued for 21 days. Fibrotic progression was evaluated through biochemical and histological assessments, including quantification of hydroxyproline content, α-smooth muscle actin (α-SMA) expression, collagen deposition percentage, and histopathological examination of lung tissue. Molecular analyses revealed that sacubitril/valsartan significantly downregulated the expression of long non-coding RNA SNHG-16 and concurrently upregulated miR-455 levels. These changes were associated with suppression of the Notch-2/Smad-3 signaling pathway. Additionally, sacubitril/valsartan treatment resulted in a notable reduction in pulmonary levels of transforming growth factor-β (TGF-β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), indicating attenuation of both fibrotic and inflammatory responses. Collectively, these findings suggest that sacubitril/valsartan mitigates pulmonary fibrosis through modulation of the SNHG-16/miR-455 axis and inhibition of the Notch-2/Smad-3/TGF-β signaling cascade, highlighting its potential as a promising therapeutic strategy for the management of pulmonary fibrosis.
如何引用
AMA
Zeinab M Abdel-Nasser, Mai A Zaafan. Sacubitril/valsartan as a modulator of pulmonary fibrosis: insights into Lnc-SNHG-16/miR-455 modulation and Notch/Smad-3 pathway inhibition.. Naunyn-Schmiedeberg's archives of pharmacology. 2026; doi:10.1007/s00210-026-05034-0.
APA
Zeinab M Abdel-Nasser, Mai A Zaafan (2026). Sacubitril/valsartan as a modulator of pulmonary fibrosis: insights into Lnc-SNHG-16/miR-455 modulation and Notch/Smad-3 pathway inhibition.. Naunyn-Schmiedeberg's archives of pharmacology. https://doi.org/10.1007/s00210-026-05034-0
GB/T 7714
Zeinab M Abdel-Nasser, Mai A Zaafan. Sacubitril/valsartan as a modulator of pulmonary fibrosis: insights into Lnc-SNHG-16/miR-455 modulation and Notch/Smad-3 pathway inhibition.[J]. Naunyn-Schmiedeberg's archives of pharmacology, 2026 doi:10.1007/s00210-026-05034-0.
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