Fakir Saikat, Kubra Khadeja-Tul, Akhter Mohammad Shohel, Uddin Mohammad Afaz, Barabutis Nektarios
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.
Int J Pept Res Ther. 2024;30(6). doi: 10.1007/s10989-024-10653-3. Epub 2024 Oct 1.
GHRH is produced in the hypothalamus and affects various tissues beyond the pituitary, including the lungs. GHRH antagonists exert anti-inflammatory properties in several experimental models of disease, but their role inprotecting the endothelial barrier during inflammation is less understood. This study investigates the effects ofGHRHAnt on LPS-induced endothelial dysfunction.
BPAEC and HMVEC-L cells were exposed to LPS to induce endothelial injury. GHRHAnt was administered eitherpre- or post-LPS treatment. Western blot analysis was used to evaluate protein expression levels. Paracellularpermeability was assessed utilizing FITC-dextran assay to evaluate endothelial barrier function.
GHRHAnt post-treatment significantly reduced LPS-induced MLC2 phosphorylation and cofilin activation inBPAECs. Furthermore, pretreatment with GHRHAnt enhanced barrier function and ameliorated LPS-inducedhyperpermeability in both human and bovine endothelial cells.
GHRHAnt treatment mitigates LPS-induced endothelial barrier dysfunction. These findings suggest that GHRHAntcould serve as potential therapeutic agents towards endothelial dysfunction-related illness (e.g. sepsis).
生长激素释放激素（GHRH）在下丘脑产生，并影响垂体以外的各种组织，包括肺。生长激素释放激素拮抗剂在多种疾病实验模型中发挥抗炎特性，但其在炎症期间保护内皮屏障的作用尚不清楚。本研究调查了生长激素释放激素拮抗剂（GHRHAnt）对脂多糖（LPS）诱导的内皮功能障碍的影响。
将牛肺动脉内皮细胞（BPAEC）和人微血管内皮细胞（HMVEC-L）暴露于LPS以诱导内皮损伤。在LPS处理前或处理后给予GHRHAnt。采用蛋白质印迹分析评估蛋白质表达水平。利用异硫氰酸荧光素（FITC）-葡聚糖测定法评估细胞旁通透性，以评估内皮屏障功能。
GHRHAnt处理后显著降低了LPS诱导的BPAEC中肌球蛋白轻链2（MLC2）磷酸化和丝切蛋白激活。此外，GHRHAnt预处理增强了人和牛内皮细胞的屏障功能，并改善了LPS诱导的高通透性。
GHRHAnt治疗减轻了LPS诱导的内皮屏障功能障碍。这些发现表明，GHRHAnt可作为治疗内皮功能障碍相关疾病（如脓毒症）的潜在治疗药物。
