Department of Anesthesiology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, China.
Department of Anesthesiology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, China.
Biochem Biophys Res Commun. 2018 Nov 30;506(3):504-509. doi: 10.1016/j.bbrc.2018.10.105. Epub 2018 Oct 22.
Fat embolism syndrome (FES) is a serious complication after trauma, surgery and fat emulsion input and can lead to serious pulmonary injury. Autophagy controls the cell survival and homeostasis by removing the mis-folded proteins and damaged organelles as well as intracellular pathogens through a lysosomal degradation pathway. Increasing research documented that autophagy was wildly involved in variety of human diseases and had huge therapeutic potential. However, the role and mechanism of autophagy in FES remains largely unknown. The rat model of FES was established by tail vein injection with fat and was assessed by Wet-to-Dry (W/D) ratio analysis, hematoxylin-eosin (HE) analysis, staining Oil red staining analysis and qPCR analysis. Western blots were employed to detect the expression of autophagy markers. The changes of pulmonary injury were observed after premedication of rapamycin (an autophagy activator). The alveolar structural damage, red free fat substances in the blood vessels of lung, increased the lung ratio, and the up-regulated MPO expression and activity were showed in the FES models. The expressions of autophagy markers were decreased and meanwhile, apoptosis markers were increased in the FES model. Rapamycin restored the expression of autophagy markers and inhibited the apoptosis and further, resulting in the improvement of the pulmonary injury. Thus, our study demonstrated that autophagy was inhibited and apoptosis was promoted in FES and further Rapamycin alleviated the pulmonary damage in FES via restoring the autophagy and inhibiting the apoptosis.
脂肪栓塞综合征（FES）是创伤、手术和脂肪乳剂输入后的一种严重并发症，可导致严重的肺损伤。自噬通过溶酶体降解途径清除错误折叠的蛋白质和受损的细胞器以及细胞内病原体，从而控制细胞的存活和稳态。越来越多的研究表明，自噬广泛参与多种人类疾病，并具有巨大的治疗潜力。然而，自噬在 FES 中的作用和机制在很大程度上仍不清楚。通过尾静脉注射脂肪建立 FES 大鼠模型，并通过湿重/干重（W/D）比分析、苏木精-伊红（HE）分析、油红染色分析和 qPCR 分析进行评估。采用 Western blot 检测自噬标志物的表达。预先给予雷帕霉素（自噬激活剂）后观察肺损伤的变化。FES 模型中观察到肺泡结构损伤、血管中无血色的游离脂肪物质增加、肺比增加以及 MPO 表达和活性上调。自噬标志物的表达降低，同时 FES 模型中凋亡标志物增加。雷帕霉素恢复了自噬标志物的表达，抑制了凋亡，从而改善了肺损伤。因此，我们的研究表明，FES 中自噬受到抑制，凋亡受到促进，而雷帕霉素通过恢复自噬和抑制凋亡减轻 FES 中的肺损伤。
