乌司他丁对脓毒症大鼠脏器保护的代谢组学研究

目的基于HPLC/MS技术从代谢组学角度探讨乌司他丁对脓毒症大鼠脏器的保护作用的可能机制。方法将30只雄性Wistar大鼠随机等分为对照组、脓毒症组、乌司他丁(UTI)组。采用盲肠结扎穿孔术(CLP)复制脓毒症大鼠模型;对照组行开腹、关腹,不予CLP。UTI组于制模前1h肌肉注射UTI10万U/kg,脓毒症组及对照组给予平衡液5mL/kg。术后12h断尾法采集3组大鼠外周血0.5mL,静置、离心后收集血清。其次采用HPLC/MS分析大鼠血清代谢特征,进而分析UTI预处理对脓毒症大鼠血清中不饱和脂肪酸浓度的影响。结果主成分分析(PCA)可完全区分3组大鼠的生理特征。UTI组不饱和脂肪酸的浓度相对于脓毒症组明显升高且趋向于对照组甚至高于对照组。结论 UTI预处理能提高血液中参与能量代谢的不饱和脂肪酸浓度,对脓毒症大鼠能量代谢有重要的改善作用。

Objective To investigate the possible mechanism of the protection of Ulinastadin （UTI） on the organs in septic rats in terms of the metabolomics based on the High Performance Liquid Chromatography/Mass Spectrometry/Mass Spectrometry （HPLC/MS） technology. Methods Thirty male Wistar rats were randomLy equally assigned to control group, sepsis group and UTI group. The rats of UTI group were intramuscular injected with UTI（10×104U/kg） an hour before Cecal ligation and puncture （CLP）. However, rats of sepsis group or control group were injected with balanced solution （5mL/kg）. Septic rat models were established by cecal ligation and perforation （CLP）. The rats of control group only experienced a simulated operation not CLP. 0.5mL blood of each rats was drawn by tail breaking method, then was kept still for a moment and serum was collected after centrifugation. What is more, the metabolic characteristics of serum were analyzed by HPLC/MS and then the effect of UTI on the concentration of unsaturated fatty acid was analyzed. Results Physiological characteristic of each group rats can be completely distinguished by principal component （PCA） analysis from other groups. The concentration of unsaturated fatty acid of rats under the UTI treatment was significantly elevated compare to the rats of sepsis group, moreover, toward to the rats of control group and even higher than it. Conclusion UTI can increase the consistency of unsaturated fatty acid in the blood which take part in the energy metabolism and play an important in improving the energy metabolism of septic rats.