高原高寒条件下烧伤大鼠代谢指纹图谱绘制及代谢标志物筛选  

Metabolic fingerprint and identification of metabolic markers in burned rats exposed to plateau and cold conditions

作  者:张勇[1] 张立森 岳良 张磊磊[1] 柯海文 沈运彪 Zhang Yong;Zhang Lisen;Yue Liang;Zhang Leilei;Ke Haiwen;Shen Yunbiao(Center of Burns and Plastic Surgery,General Hospital of Xinjiang Military Command,Urumqi 830000,China)

机构地区:[1]新疆军区总医院烧伤整形中心,乌鲁木齐830000

出  处:《中华损伤与修复杂志(电子版)》2025年第1期42-54,共13页Chinese Journal of Injury Repair and Wound Healing(Electronic Edition)

基  金:新疆维吾尔自治区自然科学基金面上项目(2020D01A140)。

摘  要:目的利用代谢组学技术分析高海拔地区、寒冷条件下重度烧伤大鼠的代谢变化规律,绘制高原及高原烧伤大鼠代谢指纹图谱,筛选潜在代谢标志物,为制定高原地区烧伤营养治疗方案提供依据。方法选择60只健康雄性SD大鼠,随机分为非高原非烧伤组、高原非烧伤组及高原烧伤组,设置建模后第1、3、7、14天为观察时点,每组各时点5只大鼠。高原非烧伤组及高原烧伤组大鼠在西北特殊环境模拟舱内模拟海拔5000 m的高原条件喂养,在高原烧伤组制作30%总体表面积(TBSA)Ⅲ度烧伤大鼠模型。在建模后第1、3、7、14天,采集各组大鼠血液标本并通过高效液相色谱-串联质谱(HPLC-MS/MS)法进行检测,运用主成分分析(PCA)、正交偏最小二乘法判别分析(OPLSDA)数据建模和判别技术绘制高原及高原烧伤大鼠代谢指纹图谱,通过Z-score、火山图、箱形图分析方法筛选高原及高原烧伤大鼠相关代谢标志物。结果与非高原非烧伤组相比,高原非烧伤组和高原烧伤组各时点代谢物均出现明显聚类,成功绘制高原及高原烧伤大鼠代谢指纹图谱。在模拟高原大鼠筛选出118个高表达代谢物(D-麦芽糖、甘氨酸、烟酰胺核糖等)及101个低表达代谢物(水苏碱、甘露醇、山梨醇等)。在高原烧伤大鼠筛选出甘氨酸、2-乙基-2-羟基丁酸、D-2,3-二羟基丙酸、亮氨酸、2-羟基己酸、3-羟基丁酸、尿嘧啶、L-组氨酸及半胱氨酸硫酸酯等作为潜在代谢标志物。结论应用代谢组学方法成功绘制高原特殊条件下重度烧伤大鼠代谢指纹图谱,筛选出的代谢物可能是高原特殊环境和高原烧伤相关的潜在标志物。Objective To understand the metabolic changes of severe burn rats under plateau and cold conditions by metabolomics technology,map the metabolic fingerprint of rats or burn rats in plateau environment,screen potential metabolic markers,and provide evidence for the development of nutritional treatment of burn at high altitude.Methods A total of 60 healthy male SD rats were randomly divided into non-plateau control group,plateau group and plateau burn group.The 1st,3rd,7th,and 14th day after establishing model were set as the observation phase points,with 5 experimental rats at each time.Rats in plateau group and plateau burn group were fed in a simulated plateau condition of 5000 meters above sea level in a special environment simulation chamber in northwest China.Rat models with a 30% total body surface area(TBSA)full-thickness burn were established in plateau burn group.Blood samples from each group were collected and detected by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)at 1,3,7,14 d after the model was established.Principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were used to draw metabolic fingerprints of plateau rats and plateau burn rats.Metabolic markers related to altitude and altitude burn were screened by Z-score,volcano plot and box-plot analysis.Results Compared with the non-plateau control group,the metabolites in the plateau rats and the plateau burn rats showed obvious clustering at each time point,and the metabolic fingerprints of the plateau rats and the plateau burn rats were successfully mapped.A total of 118 metabolites with high expression(mainly included D-maltose,glycine,nicotinamide ribose)and 101 metabolites with low expression(mainly included perilline,mannitol,sorbitol)were selected in the plateau rats.Glycine,2-ethyl-2-hydroxybutyric acid,D-2,3-dihydroxypropionic acid,leucine,2-hydroxycaproic acid,3-hydroxybutyric acid,uracil,L-histidine and cysteine sulfate were selected as potential metabolic markers i

关 键 词:重症烧伤 高原 寒冷 代谢组学 指纹图谱 代谢标志物 

分 类 号:R28[医药卫生—中药学]

 

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