基于代谢组学方法研究中段小肠切除大鼠模型发生术后疲劳的机制
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摘要
目的运用代谢组学方法研究中段小肠切除大鼠模型发生术后疲劳的机制。方法雄性SD大鼠20只随机分为模型组与正常组,利用LC-MS(液相色谱-质谱联用)获取大鼠血浆代谢图谱,并采用主成分分析(PCA)、偏最小二乘法-判别分析(PLS-DA)进行多变量统计分析,筛选出区分术后疲劳大鼠与正常大鼠的重要差异代谢物及相关代谢途径。结果术后疲劳大鼠与正常大鼠相比,得到差异性代谢离子5 680个,两组大鼠血浆代谢谱存在明显差异,同时色氨酸代谢,戊糖和葡萄糖醛酸的相互转化,精氨酸和脯氨酸代谢,细胞色素P450对外源化合物代谢的影响,卟啉和叶绿素、叶酸合成、维生素B6、亚油酸代谢等代谢通路存在明显差异。结论中段小肠切除大鼠模型发生术后疲劳与色氨酸、精氨酸、戊糖和葡萄糖醛酸的相互转化等代谢途径变化引起的脑内5-HT合成增多、血液循环功能减弱、能量供给障碍相关。由于目前非靶向代谢物的鉴定仍有不足,具体各种代谢物定性及定量分析仍需进一步实验研究。
Objective To study the mechanism of postoperative fatigue in a rat model of middle small intestine resection using metabolomics methodology. Methods Twenty male Sprague-Dawley rats were randomly divided into model group and normal group. LC-MS(liquid chromatography-mass spectrometry)was used to obtain plasma metabolic profiles of rats,and principal component analysis(PCA)and partial least squares method-Discriminant analysis(PLS-DA)for multivariate statistical analysis,screening for important differential metabolites and related metabolic pathways between postoperative fatigue rats and normal rats. Results Compared with normal rats,postoperative fatigue rats obtained 5 680 differential metabolic ions. There were significant differences in plasma metabolic profiles between the two groups. At the same time,tryptophan metabolism,pentose and glucuronate interconversions,arginine and proline metabolism,metabolism of xenobiotics by cytochrome P450,porphyrin and chlorophyll metabolism,folate biosynthesis,vitamin B6,linoleic acid metabolic pathways were significantly different in the 2 groups. Conclusions The mechanism of postoperative fatigue in the rat model of middle small intestine resection may be related to the increase of 5-HT synthesis and blood circulation in the brain caused by the changes of metabolic pathways such as the conversion of tryptophan,arginine,pentose and glucuronic acid,attenuation,energy supply barriers,etc. Because the identification of non-targeted metabolites is still insufficient,the qualitative and quantitative analysis of specific metabolites still needs further experimental research.
Objective To study the mechanism of postoperative fatigue in a rat model of middle small intestine resection using metabolomics methodology. Methods Twenty male Sprague-Dawley rats were randomly divided into model group and normal group. LC-MS(liquid chromatography-mass spectrometry)was used to obtain plasma metabolic profiles of rats,and principal component analysis(PCA)and partial least squares method-Discriminant analysis(PLS-DA)for multivariate statistical analysis,screening for important differential metabolites and related metabolic pathways between postoperative fatigue rats and normal rats. Results Compared with normal rats,postoperative fatigue rats obtained 5 680 differential metabolic ions. There were significant differences in plasma metabolic profiles between the two groups. At the same time,tryptophan metabolism,pentose and glucuronate interconversions,arginine and proline metabolism,metabolism of xenobiotics by cytochrome P450,porphyrin and chlorophyll metabolism,folate biosynthesis,vitamin B6,linoleic acid metabolic pathways were significantly different in the 2 groups. Conclusions The mechanism of postoperative fatigue in the rat model of middle small intestine resection may be related to the increase of 5-HT synthesis and blood circulation in the brain caused by the changes of metabolic pathways such as the conversion of tryptophan,arginine,pentose and glucuronic acid,attenuation,energy supply barriers,etc. Because the identification of non-targeted metabolites is still insufficient,the qualitative and quantitative analysis of specific metabolites still needs further experimental research.
引文
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[11]王斌. L-精氨酸的抗疲劳作用研究[J].氨基酸和生物资源,2018,30(2):44-47.
[2] LU Y,NING H,JIANG X,et al. Metabolomics reveals hippocampal metabolic fluctuations of postoperative fatigue syndrome and anti-fatigue effect of Carthamus tinctorius L extract in rat model[J]. Biomed Chromatogr,2017,30(7):1052-1058.
[3] LU Y,YANG R,JIANG X,et al. Serum metabolite profiles of postoperative fatigue syndrome in rat following partial hepatectomy[J]. Clin Biochem Nutr,2016,58(3):210-215.
[4]梁雪芳,冯婉仪,温丹婷,等.艾灸治疗术后疲劳综合征的随机对照研究[J].实用医学杂志,2013,29(18):3074-3075.
[5] ZHUANG C L,MAO X Y,LIU S,et al. Ginsenoside Rb1 improves postoperative fatigue syndrome by reducing skeletal muscle oxidative stress through activation of the PI3K/Akt/Nrf2 pathway in aged rats[J]. Eur J Pharmacol,2014,740:480-487.
[6]陈红燕,庞凤舜,经宝.降浊升清颗粒对术后疲劳大鼠模型的影响[J].中华普通外科学文献,2017,11(6):370-374.
[7]余震,章晓东,陈震,等.术后疲劳综合征动物模型的建立及其评价[J].肠外与肠内营养,2009,16(2):100-104.
[8] NICHOLSON J K,CONNELLY J,LINDON J C,et al. Metabonomics:a platform for studying drug toxicity and gene function[J]. Nat Rev Drug Discov,2002,1(2):153-161.
[9] WILSON M,MAUGHAN R J. Evidence for a possible role o f 5-HT in the genesis of fatigue in man[J]. Exp Physiol,1992,77:921-924.
[10] CHEN W Z,LIU S,CHEN F F,et al. Prevention of postoperative fatigue syndrome in rat model by ginsenoside Rb1 via downregulation of inflammation along the NMDA receptor pathway in the hippocampus[J]. Biol Pharm Bull,2015,38(2):239-47.
[11]王斌. L-精氨酸的抗疲劳作用研究[J].氨基酸和生物资源,2018,30(2):44-47.