1 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
2 Department of Anatomy and Histology, School of Basic Medical Sciences, Peking University, Beijing, China.
Cell Transplant. 2019 Jun;28(6):704-712. doi: 10.1177/0963689718814766. Epub 2018 Nov 19.
Fat embolism syndrome (FES) is a common complication following long bone fracture; fat droplets are released into the blood circulation and form embolisms, mainly in lung and brain. However, the potential mechanisms involved remain to be clarified. In this study, the mechanism of brain injury following FES and the protective effects of urinary trypsin inhibitor (UTI)-a serine protease inhibitor-were investigated. Sixty male Sprague-Dawley rats were divided randomly into sham, FES and FES+UTI treatment groups. The FES model was established using tail vein injection of glycerol trioleate, and UTI was administered by intraperitoneal injection immediately following FES. Brain/lung water content evaluation, Evans blue content and magnetic resonance imaging examination were used to assess the effects of UTI. Furthermore, immunohistochemistry and western blot were also applied to explore the protective mechanism of UTI following FES. The results of oil red O staining indicated that the FES model was successfully established. UTI could significantly attenuate blood-brain-barrier (BBB) disruption, as seen through brain edema evaluation and Evans blue content examination. Immunofluorescence staining results indicated that the TLR4-JNK pathway was involved in brain injury after FES; this effect could be quenched by UTI treatment. Furthermore, UTI could decrease the levels of downstream target proteins of the TLR4-JNK pathway, phosphorylated-NF- κB (p65) and p53 in brain. Our results showed that UTI could alleviate BBB injury after FES through blocking activity of the TLR4-JNK pathway.
脂肪栓塞综合征（FES）是长骨骨折后的常见并发症；脂肪滴释放到血液循环中并形成栓塞，主要在肺和脑中。然而，涉及的潜在机制仍需阐明。在这项研究中，研究了 FES 后脑损伤的机制以及尿胰蛋白酶抑制剂（UTI）-一种丝氨酸蛋白酶抑制剂的保护作用。60 只雄性 Sprague-Dawley 大鼠随机分为假手术、FES 和 FES+UTI 治疗组。使用甘油三油酸酯尾静脉注射建立 FES 模型，并在 FES 后立即通过腹腔注射给予 UTI。通过评估脑/肺水含量、伊文思蓝含量和磁共振成像检查来评估 UTI 的作用。此外，还应用免疫组织化学和蛋白质印迹法来探讨 UTI 对 FES 后保护作用的机制。油红 O 染色的结果表明成功建立了 FES 模型。UTI 可明显减轻血脑屏障（BBB）破坏，通过脑水肿评估和伊文思蓝含量检查可见。免疫荧光染色结果表明，TLR4-JNK 通路参与了 FES 后的脑损伤；UTI 治疗可抑制这种作用。此外，UTI 可降低 TLR4-JNK 通路下游靶蛋白磷酸化-NF-κB（p65）和 p53 在脑内的水平。我们的研究结果表明，UTI 可通过阻断 TLR4-JNK 通路的活性来减轻 FES 后 BBB 损伤。
