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升结肠支架相关性腹膜炎(CASP)在脓毒症大鼠模型中引发过度炎症和全身代谢功能障碍。

Colon Ascendens Stent Peritonitis (CASP) Induces Excessive Inflammation and Systemic Metabolic Dysfunction in a Septic Rat Model.

机构信息

CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences (CAS) , Wuhan 430071, China.

Research Institute of General Surgery, General Hospital of Nanjing Military Region , Nanjing, Jiangsu 210002, China.

出版信息

J Proteome Res. 2018 Jan 5;17(1):680-688. doi: 10.1021/acs.jproteome.7b00730. Epub 2017 Dec 15.

DOI:10.1021/acs.jproteome.7b00730
PMID:29205045
Abstract

The colon ascendens stent peritonitis (CASP) surgery induces a leakage of gut contents, causing polymicrobial sepsis related to post-operative multiple organ failure and death in surgical patient. To evaluate the effects of CASP on multiple organs, we analyzed the systemic metabolic consequences in liver, kidney, lung, and heart of rats after CASP by employing a combination of metabolomics, clinical chemistry, and biological assays. We found that CASP surgery after 18 h resulted in striking elevations of lipid, amino acids, acetate, choline, PC, and GPC in rat liver together with significant depletion of glucose and glycogen. Marked elevations of organic acids including lactate, acetate, and creatine and amino acids accompanied by decline of glucose, betaine, TMAO, choline metabolites (PC and GPC) nucleotides, and a range of organic osmolytes such as myo-inositol are observed in the kidney of 18 h post-operative rat. Furthermore, 18 h post-operative rats exhibited accumulations of lipid, amino acids, and depletions of taurine, myo-inositol, choline, PC, and GPC and some nucleotides including uridine, inosine, and adenosine in the lung. In addition, significant elevations of some amino acids, uracil, betaine, and choline metabolites, together with depletion of inosine-5'-monophosphate, were only observed in the heart of 18 h post-operative rats. These results provide new insights into pathological consequences of CASP surgery, which are important for timely prognosis of sepsis.

摘要

升结肠支架腹膜炎(CASP)手术会导致肠道内容物泄漏,引起手术后多器官衰竭和死亡的与多种微生物有关的败血症。为了评估 CASP 对多个器官的影响,我们通过代谢组学、临床化学和生物测定相结合的方法,分析了 CASP 后大鼠肝、肾、肺和心脏的全身代谢后果。我们发现,CASP 手术后 18 小时,大鼠肝内脂质、氨基酸、乙酸盐、胆碱、PC 和 GPC 显著升高,同时葡萄糖和糖原明显减少。术后 18 小时,大鼠肾内显著升高的有机酸包括乳酸、乙酸和肌酸以及氨基酸,同时葡萄糖、甜菜碱、TMAO、胆碱代谢物(PC 和 GPC)核苷酸以及一系列有机渗透物如肌醇下降。此外,术后 18 小时的大鼠肺中积累了脂质、氨基酸,同时 taurine、肌醇、胆碱、PC 和 GPC 以及一些核苷酸如尿苷、次黄嘌呤和腺苷减少。此外,术后 18 小时的大鼠心脏中仅观察到一些氨基酸、尿嘧啶、甜菜碱和胆碱代谢物的显著升高,同时肌苷-5'-单磷酸减少。这些结果为 CASP 手术的病理后果提供了新的见解,这对败血症的及时预后很重要。

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