OBJECTIVE To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs). METHODS Mice were randomly divided into control, LPS, and crocin + LPS (15, 30, and 60 mg/kg) groups. HUVECs were separated into eight groups: control, crocin, matrix metalloproteinase 9 inhibitor (MMP-9 inhib), cathepsin L inhibitor (CTL inhib), LPS, MMP-9 inhib + LPS, CTL inhib + LPS, and crocin + LPS. The potential cytotoxic effect of crocin on HUVECs was mainly evaluated through methylthiazolyldiphenyl-tetrazolium bromide assay. Histological changes were assessed via hemotoxylin and eosin staining. Lung capillary permeability was detected on the basis of wet-dry ratio and through fluorescein isothiocyanate-albumin assay. Then, protein levels were detected through Western blot analysis, immunohistochemical staining, and immunofluorescence. RESULTS This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. Crocin also protected against the degradation of endothelial glycocalyx heparan sulfate and syndecan-4 by inhibiting the expressions of CTL, heparanase, and MMP-9 in vivo and in vitro. Overall, this study revealed the protective effects of crocin on LPS-induced ARDS and elaborated their underlying mechanism. CONCLUSION Crocin alleviated LPS-induced ARDS by protecting against glycocalyx damage and suppressing inflammatory signaling pathways.

中文翻译：

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番红花通过防止糖萼损伤和抑制炎症信号通路减轻脂多糖诱导的急性呼吸窘迫综合征。

目的探讨番红花抗脂多糖（LPS）诱导的急性呼吸窘迫综合征（ARDS）小鼠和LPS刺激的人脐静脉内皮细胞（HUVECs）糖萼损伤和炎性损伤的机制。方法将小鼠随机分为对照组，LPS和crocin + LPS（15、30和60 mg / kg）组。HUVEC分为八组：对照，crocro，基质金属蛋白酶9抑制剂（MMP-9 inhib），组织蛋白酶L抑制剂（CTL inhib），LPS，MMP-9 inhib + LPS，CTL inhib + LPS和crocin + LPS。番红花对HUVECs的潜在细胞毒性作用主要通过甲基噻唑基二苯基四唑鎓溴化物测定来评估。通过苏木精和曙红染色评估组织学变化。根据干-湿比并通过异硫氰酸荧光素-白蛋白测定检测肺毛细血管的渗透性。然后，通过蛋白质印迹分析，免疫组织化学染色和免疫荧光检测蛋白质水平。结果本研究表明，番红花可以改善LPS诱导的ARDS小鼠的肺血管通透性，并在体内和体外抑制高迁移率族盒，核因子κB和促分裂原活化蛋白激酶的炎症信号通路。Crocin还通过在体内和体外抑制CTL，乙酰肝素酶和MMP-9的表达来保护内皮糖萼硫酸乙酰肝素和syndecan-4的降解。总体而言，这项研究揭示了番红花素对脂多糖诱导的ARDS的保护作用，并阐明了其潜在机制。