Wei Yufen, Gao Na, Zhang Zhongxiao, Zu Xianpeng, Hu Zhenlin, Zhang Weidong, Yin Jun, Liu Xinru
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China; National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jul 15;1026:176-182. doi: 10.1016/j.jchromb.2015.08.009. Epub 2015 Aug 14.
Sepsis is a disease with high mortality that requires rapid diagnosis and treatment. This study used a metabolomic approach to profile the metabolic changes at the early stage of sepsis induced by cecal ligation and puncture (CLP) in rats and investigated the interventional effects of Huang-Lian-Jie-Du-Tang (HLJDT). Male SD rats were intragastrically administered 270mg/kg HLJDT 2h prior to CLP, serum extracts were profiled by liquid chromatography/quadrupole time-of-flight mass spectrometer (LC-Q-TOF-MS) and multivariate analytical (MVA) methods were employed to evaluate the metabolic changes of extracts. A Partial Least-Squares Discriminant Analysis (PLS-DA) score plot indicated that septic rats undergo significant metabolic changes 2h after CLP, and HLJDT administration could reverse the metabolic changes induced by CLP. Sixteen biomarkers involved in amino acid metabolism, unsaturated fatty acid metabolism, purine metabolism, and lipid metabolism were identified after Orthogonal Partial Least-Squares Analysis (OPLS). Among the 16 metabolites, 10 were regulated by HLJDT. This study established the foundation for further research of the early diagnosis biomarkers and therapeutic evaluation biomarkers discovery of sepsis.
脓毒症是一种死亡率很高的疾病,需要快速诊断和治疗。本研究采用代谢组学方法分析大鼠盲肠结扎穿刺(CLP)诱导的脓毒症早期的代谢变化,并研究黄连解毒汤(HLJDT)的干预作用。雄性SD大鼠在CLP前2小时灌胃给予270mg/kg HLJDT,采用液相色谱/四极杆飞行时间质谱仪(LC-Q-TOF-MS)对血清提取物进行分析,并采用多元分析(MVA)方法评估提取物的代谢变化。偏最小二乘判别分析(PLS-DA)得分图表明,脓毒症大鼠在CLP后2小时发生显著代谢变化,给予HLJDT可逆转CLP诱导的代谢变化。通过正交偏最小二乘法分析(OPLS)鉴定出16种参与氨基酸代谢、不饱和脂肪酸代谢、嘌呤代谢和脂质代谢的生物标志物。在这16种代谢物中,有10种受HLJDT调节。本研究为进一步研究脓毒症的早期诊断生物标志物和治疗评估生物标志物奠定了基础。