急性肺损伤(ALI)是一种严重且可能致命的呼吸系统疾病,治疗选择有限。ALI的病理演变是由持续性炎症驱动的,肺血管屏障的破坏和氧化应激。先前调查的证据已经确定了5α-雄激素-3β,5α,6β-三醇(三醇),天然存在的神经保护化合物胆甾烷-3β的合成类似物,5α,6β-三醇,具有显著的抗炎和抗氧化特性。然而,TRIOL对减轻肺损伤的确切作用及其机制,基本上没有被探索过。这里,TRIOL对脂多糖(LPS)诱导的肺上皮细胞和内皮细胞炎症和氧化应激损伤均表现出明显的抑制作用。这种保护作用是通过其减轻氧化应激和抑制由核因子-κB(NF-κB)协调的炎症级联反应的能力来实现的,从而保持肺上皮屏障的完整性。我们进一步验证了TRIOL可以通过减少炎症细胞浸润和改善肺水肿来减轻LPS诱导的大鼠和小鼠肺损伤。此外,TRIOL降低了LPS诱导的促炎因子,增加了抗炎因子。总之,我们的研究表明三醇是治疗ALI的一种有希望的新型候选药物。
Acute lung injury (ALI) is a severe and potentially fatal respiratory condition with limited treatment options. The pathological evolution of ALI is driven by persistent inflammation, destruction of the pulmonary vascular barrier and oxidative stress. Evidence from prior investigations has identified 5α-androst-3β,5α,6β-Triol (TRIOL), a synthetic analogue of the naturally occurring neuroprotective compound cholestane-3β,5α,6β-triol, possesses notable anti-inflammatory and antioxidative properties. However, the precise effects of TRIOL on alleviating lung injury along with the mechanisms, have remained largely unexplored. Here, TRIOL exhibited pronounced inhibitory actions on lipopolysaccharide (LPS)-induced inflammation and oxidative stress damage in both lung epithelial and endothelial cells. This protective effect is achieved by its ability to mitigate oxidative stress and restrain the inflammatory cascade orchestrated by nuclear factor-kappa B (NF-κB), thereby preserving the integrity of the pulmonary epithelial barrier. We further validated that TRIOL can attenuate LPS-induced lung injury in rats and mice by reducing inflammatory cell infiltration and improving pulmonary edema. Furthermore, TRIOL decreased the pro-inflammatory factors and increased of anti-inflammatory factors induced by LPS. In conclusion, our study presents TRIOL as a promising novel candidate for the treatment of ALI.