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帕西瑞肽对脂多糖诱导的急性肺损伤的保护作用。

Protective Effects of Pasireotide in LPS-Induced Acute Lung Injury.

作者信息

Fakir Saikat, Sarker Md Matiur Rahman, Sigdel Madan, Barabutis Nektarios

机构信息

School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, USA.

出版信息

Pharmaceuticals (Basel). 2025 Jun 22;18(7):942. doi: 10.3390/ph18070942.

Abstract

Acute lung injury (ALI) is an inflammatory condition characterized by tissue barrier damage, which leads to vascular leakage, pulmonary edema, and compromised gas exchange. Lipopolysaccharides (LPS) are a component of Gram-negative bacteria, which trigger inflammation by Toll-like receptor 4 (TLR4) activation. Herein, we investigated the possibility that Pasireotide (PAS) exerts protective effects in an experimental model of ALI. C57BL/6 male mice received an intratracheal injection of saline or LPS, followed by PAS or vehicle treatment. Bronchoalveolar lavage fluid (BALF) was collected via tracheal catheterization, and Western blot analysis was used to detect protein expression variations. Our results suggest that PAS treatment alleviates LPS-induced mouse lung injury and inflammation. JAK/STAT and MAPK activation levels in the inflamed lungs were suppressed due to PAS treatment, as well as BALF protein concentration. Additionally, PAS counteracted LPS-induced Grp94 protein reduction, suggesting the involvement of ATF6 in PAS-triggered barrier-protective effects. Grp94 is a downstream ATF6 target. Our data demonstrate that PAS protects mouse lungs against LPS in an experimental model of ALI.

摘要

急性肺损伤(ALI)是一种以组织屏障损伤为特征的炎症状态,可导致血管渗漏、肺水肿和气体交换受损。脂多糖(LPS)是革兰氏阴性菌的一种成分,可通过激活Toll样受体4(TLR4)引发炎症。在此,我们研究了帕西瑞肽(PAS)在ALI实验模型中发挥保护作用的可能性。C57BL/6雄性小鼠经气管内注射生理盐水或LPS,随后接受PAS或赋形剂治疗。通过气管插管收集支气管肺泡灌洗液(BALF),并采用蛋白质印迹分析检测蛋白质表达变化。我们的结果表明,PAS治疗可减轻LPS诱导的小鼠肺损伤和炎症。由于PAS治疗,炎症肺组织中的JAK/STAT和MAPK激活水平以及BALF蛋白浓度均受到抑制。此外,PAS可抵消LPS诱导的Grp94蛋白减少,提示ATF6参与了PAS触发的屏障保护作用。Grp94是ATF6的下游靶点。我们的数据表明,在ALI实验模型中,PAS可保护小鼠肺部免受LPS损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b908/12298338/2a481172389e/pharmaceuticals-18-00942-g001.jpg

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