Wei Bin, Zheng Jinguang, Chai Jiake, Huang Jianxiang, Duan Hongjie, Han Shaofang, Yang Xiaolin, Zhang Wenjia, Hu Fangchao, Qu Yirui, Liu Xiangyu, Liu Tian, Wu Yushou, Chi Yunfei
Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, 100048, China.
The First Department of Surgery, Chinese People's Armed Police Force Hospital of Beijing, Beijing, 100027, China.
Eur J Med Res. 2025 Jan 7;30(1):10. doi: 10.1186/s40001-024-02245-0.
Burn-hemorrhagic shock combined injury, a severe condition causing complex stress responses and metabolic disturbances that significantly affect clinical outcomes in both military and civilian settings, was modeled in swine to investigate the associated metabolomic and proteomic changes and identify potential biomarkers for disease prognosis.
Eight clean-grade adult male Landrace pigs (4-5 months, average weight 60-70 kg) were used to model burn-hemorrhagic shock combined injury. Serum samples collected at 0 h and 2 h post-injury were analyzed using metabolomic and proteomic measurements. The metabolomic and proteomic data were processed through partial least squares-discriminant analysis (PLS-DA) and the KEGG enrichment etc. Furthermore, the integrate analysis of the metabolomic and proteomic data was generalized by canonical correlation discriminant analysis, and the correlation between metabolites and mortality of the swine model was predicted using a multiple linear regression model by Pearson analysis.
PLS-DA revealed a global shift in each of the metabolomic and proteomic profiles following injury. The levels of 87 signature metabolites including various types of amino acids, fatty acids and acyl-carnitines of different lengths, and many metabolites in the gluconeogenesis, glycolysis, and tricarboxylic acid (TCA) cycle are generally increased (P < 0.05) after injury and can be used as biomarkers. Pathways related to amino acids metabolism and TCA cycle were significantly enriched (P < 0.01). In proteome analysis, we found dramatically altered (P < 0.05) levels of matrix and red blood cell-related proteins, such as type I collagen and hemoglobin. Most importantly, we found that the markedly elevated (P < 0.01) succinic acid, glutaric acid, and malic acid are closely associated (r = 0.863, 0.861, and 0.821, respectively) with injury severity by Pearson analysis, and can predict mortality using a multiple linear regression model.
The study provides compelling observations that burn-shock swine model undergoes dramatic changes in the acute phase and present a valuable panel for clinical use of prognosis.
烧伤 - 失血性休克复合伤是一种严重病症，会引发复杂的应激反应和代谢紊乱，在军事和民用环境中均会显著影响临床结局。本研究在猪身上建立该复合伤模型，以探究相关的代谢组学和蛋白质组学变化，并确定疾病预后的潜在生物标志物。
选用8头清洁级成年雄性长白猪（4 - 5个月龄，平均体重60 - 70千克）建立烧伤 - 失血性休克复合伤模型。对伤后0小时和2小时采集的血清样本进行代谢组学和蛋白质组学检测分析。代谢组学和蛋白质组学数据通过偏最小二乘判别分析（PLS - DA）和KEGG富集等方法进行处理。此外，通过典型相关判别分析对代谢组学和蛋白质组学数据进行整合分析，并使用Pearson分析的多元线性回归模型预测代谢物与猪模型死亡率之间的相关性。
PLS - DA显示伤后代谢组学和蛋白质组学图谱均发生了整体变化。包括各种类型氨基酸、不同长度脂肪酸和酰基肉碱在内的87种标志性代谢物水平，以及糖异生途径、糖酵解途径和三羧酸（TCA）循环中的许多代谢物，伤后普遍升高（P < 0.05），可作为生物标志物。与氨基酸代谢和TCA循环相关的通路显著富集（P < 0.01）。在蛋白质组分析中，我们发现基质和红细胞相关蛋白的水平发生了显著变化（P < 0.05），如I型胶原蛋白和血红蛋白。最重要的是，通过Pearson分析发现，琥珀酸、戊二酸和苹果酸显著升高（P < 0.01），且分别与损伤严重程度密切相关（r分别为0.863、0.861和0.821），并可使用多元线性回归模型预测死亡率。
该研究提供了令人信服的观察结果，即烧伤 - 休克猪模型在急性期经历了显著变化，并为临床预后提供了一个有价值的指标。
