基于核磁共振技术的临床尿毒症的代谢组学研究
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摘要
采用核磁共振技术与统计学分析方法,结合尿液的生化指标,进行临床尿毒症尿样的代谢组学研究。结果表明,尿毒症患者和健康对照人群尿样的代谢轮廓存在明显差异,通过核磁共振氢谱鉴定出70种代谢物,其中20种具有显著差异。与健康人群相比,尿毒症患者尿液中2-羟基异丁酸、3-羟基丁酸、丙酮、丁酸、谷氨酸、肌氨酸、肌酐、赖氨酸、N,N-二甲基组氨酸、柠檬酸、天冬酰胺、乙醇和乙醇胺的含量明显偏低,而支链氨基酸(包括亮氨酸、缬氨酸、异亮氨酸)、牛磺酸、乳酸、α-葡萄糖和β-葡萄糖的含量明显偏高。这些代谢物涉及氨基酸代谢、能量代谢和脂质代谢中的多条代谢途径,可作为尿毒症代谢影响的潜在的生物标志物,有助于理解尿毒症发病的生化机制。
At present,little is known about metabolic mechanism of uremia. In this study,uremia was investigated by combination of NMR spectroscopy,statistical analysis and urinary biochemical assays to provide the basis of the metabolic characteristics of uremia. The characteristic metabolites of uremia were identified from the urine of the uremia patients. The results showed that the urinary levels of2-hydroxyisobutyrate, 3-hydroxybutyrate, acetone, butyrate, glutamate, sarcosine, creatinine, lysine,N,N-dimethylglycine,citrate,asparagine,ethanol and ethanolamine were reduced,while the urinary levels of branched-chain amino acids( including leucine,valine and isoleucine),taurine,lactate and glucose were higher in uremia patients than that in the healthy subjects. The corresponding disturbed metabolic pathways were derived from the characteristic metabolites,in which amino acid,energy and lipid metabolisms were involved. The specific characteristic metabolites will help to understand the underlying biochemical mechanisms of the onset of uremia.
At present,little is known about metabolic mechanism of uremia. In this study,uremia was investigated by combination of NMR spectroscopy,statistical analysis and urinary biochemical assays to provide the basis of the metabolic characteristics of uremia. The characteristic metabolites of uremia were identified from the urine of the uremia patients. The results showed that the urinary levels of2-hydroxyisobutyrate, 3-hydroxybutyrate, acetone, butyrate, glutamate, sarcosine, creatinine, lysine,N,N-dimethylglycine,citrate,asparagine,ethanol and ethanolamine were reduced,while the urinary levels of branched-chain amino acids( including leucine,valine and isoleucine),taurine,lactate and glucose were higher in uremia patients than that in the healthy subjects. The corresponding disturbed metabolic pathways were derived from the characteristic metabolites,in which amino acid,energy and lipid metabolisms were involved. The specific characteristic metabolites will help to understand the underlying biochemical mechanisms of the onset of uremia.
引文
1 Christoffersen C,Bartels E D,Aarup A,Nielsen L B,Pedersen T X.Eur.J.Pharmacol.,2017,816(53):154-160
2 Smogorzewski M J.J.Ren.Nutr.,2017,27(6):465-469
3 Ho K J,Xue H,Mauro C R,Nguyen B,Yu P,Tao M,Seidman M A,Brunelli S M,Ozaki C K.J.Surg.Res.,2013,179(1):175-182
4 CHEN Hong-Yun.Healthy People,2014,8(23):178-179谌红云.大家健康,2014,8(23):178-179
5 Lin Y J,Guo H R,Chang Y H,Kao M T,Wang H H,Hong R I.Sens.Actuators B,2001,76(1-3):177-180
6 Yang C C,Chen T C,Wu C S,Cheng B C,Lam K K,Chien Y S,Chuang F R,Lee C T.Gend.Med.,2010,7(5):451-457
7 Wong G,Howard K,Chapman J R,Tong A,Bourke M J,Hayen A,Macaskill P,Hope R L,Williams N,Kieu A.BMC Public Health,2011,11(1):516
8 Wong M C Y,Piaggio G,Damasio M B,Molinelli C,Ferretti S M,Pistorio A,Ghiggeri G,Degl'Innocenti M L,Canepa A,Incarbone V,Mattioli G.J.Pediatr.Urol.,2018,14(1):68 e61-68 e66
9 Madsen M,Aarup A,Albinsson S,Hartvigsen K,Sorensen C M,Turczynska K,Nielsen L B,Pedersen T X.Atherosclerosis,2017,257:64-70
10 Mc Intire K L,Chen Y,Sood S,Rabkin R.Kidney Int.,2014,85(2):374-382
11 Chen Y,Biada J,Sood S,Rabkin R.Kidney Int.,2010,78(1):89-95
12 Kumar K U,Rao N M,Naidu M P.Int.J.Clin.Surg.,2014,2(4):148-158
13 WANG Zhong-Hua,HE Bing-Shu,SUN Cheng-Long,HE Jiu-Ming,ZHANG Rui-Ping,ABLIZ Zeper.Chinese J.Anal.Chem.,2018,46(3):406-412王中华,何秉淑,孙成龙,宋肖炜,贺玖明,张瑞萍,再帕尔·阿不力孜.分析化学,2018,46(3):406-412
14 Mahmoodpoor F,Rahbar Saadat Y,Barzegari A,Ardalan M,Zununi Vahed S.Biomed.Pharmacother.,2017,93:412-419
15 Wanchai K,Pongchaidecha A,Chatsudthipong V,Chattipakorn S C,Chattipakorn N,Lungkaphin A.Am.J.Med.Sci.,2017,353(1):59-69
16 HU Yong-Sheng,XU Peng-Tao,YE Sheng-Jie,SHI Wen-Yu,GAO Hong-Chang,ZHUO Yang,ZHAO Liang-Cai.Chinese J.Anal.Chem.,2018,46(2):170-177胡永胜,徐鹏涛,叶胜捷,施雯宇,高红昌,卓阳,赵良才.分析化学,2018,46(2):170-177
17 LIU Lai-Lai,DUAN Juan.J.Yunnan Univ.Tradit.Chin.Med.,2013,36(4):93-95刘莱莱,段娟.云南中医学院学报,2013,36(4):93-95
18 Awadh M A,Mohamed K A,Ahmed E A M,Amira A B,Marwa S M D.Saudi J.Biol.Sci.,2015,22(3):302-311
19 Simon C,Elizabeth S.Anaesth.Intensive.Care Med.,2006,7(2):46-48
20 Barrak M P.Clin.Lab.Med.,2015,35(3):487-502
21 Li Z,Lin C,Xu J,Wu H,Feng J,Huang H.Anal.Biochem.,2015,477:105-114
22 Lin C,Wei Z,Cheng K K,Xu J,Shen G,She C,Zhong H,Chang X,Dong J.Sci.Rep.,2017,7(1):6820
23 Ji L L,Miller R H,Nagle F J,Lardy H A,Stratman F W.Metabolism,1987,36(8):748-752
24 Lee C C,Watkins S M,Lorenzo C,Wagenknecht L E,Il'Yasova D,Chen Y I,Haffner S M,Hanley A J.Diabetes Care,2016,39(4):582-588
25 Edmonds M S,Baker D H.J.Anim.Sci.,1987,65(3):699-705
26 Gatnau R,Zimmerman D R,Nissen S L,Wannemuehler M,Ewan R C.J.Anim.Sci.,1995,73(1):159-165
27 Iida A.Nat.Genet.,2005,37(2):138-144
28 WANG Meng,LIU Ming,GUO Lin.Chin.J.Clin.Lab.Sci.,2013,31(6):401-405王萌,刘明,郭健.临床检验杂志,2013,31(6):401-405
29 Klasing K C,Barnes D M.J.Nutr.,1988,118(9):1158-1164
30 Ito T,Yoshikawa N,Inui T,Miyazaki N,Schaffer S W,Azuma J.PLo S One,2014,9(9):e107-e109
31 Mac Lellan D L,Mataija D,Doucette A,Huang W,Langlois C,Trottier G,Burton I W,Walter J A,Karakach T K.Mol.Bio Syst.,2011,7(7):2181-2188
32 Canani R B,Di Costanzo M,Leone L.Clin.Epigenetics,2012,4(1):4
33 Plecko B,Stoeckler-Ipsiroglu S,Schober E,Harrer G,Mlynarik V,Gruber S,Moser E,Moeslinger D,Silgoner H,Ipsiroglu O.Pediatr.Res.,2002,52(2):301-306
34 Kiss Z,Mukherjee J J,Crilly K S,Chung T.Febs J.,2015,250(2):395-402
2 Smogorzewski M J.J.Ren.Nutr.,2017,27(6):465-469
3 Ho K J,Xue H,Mauro C R,Nguyen B,Yu P,Tao M,Seidman M A,Brunelli S M,Ozaki C K.J.Surg.Res.,2013,179(1):175-182
4 CHEN Hong-Yun.Healthy People,2014,8(23):178-179谌红云.大家健康,2014,8(23):178-179
5 Lin Y J,Guo H R,Chang Y H,Kao M T,Wang H H,Hong R I.Sens.Actuators B,2001,76(1-3):177-180
6 Yang C C,Chen T C,Wu C S,Cheng B C,Lam K K,Chien Y S,Chuang F R,Lee C T.Gend.Med.,2010,7(5):451-457
7 Wong G,Howard K,Chapman J R,Tong A,Bourke M J,Hayen A,Macaskill P,Hope R L,Williams N,Kieu A.BMC Public Health,2011,11(1):516
8 Wong M C Y,Piaggio G,Damasio M B,Molinelli C,Ferretti S M,Pistorio A,Ghiggeri G,Degl'Innocenti M L,Canepa A,Incarbone V,Mattioli G.J.Pediatr.Urol.,2018,14(1):68 e61-68 e66
9 Madsen M,Aarup A,Albinsson S,Hartvigsen K,Sorensen C M,Turczynska K,Nielsen L B,Pedersen T X.Atherosclerosis,2017,257:64-70
10 Mc Intire K L,Chen Y,Sood S,Rabkin R.Kidney Int.,2014,85(2):374-382
11 Chen Y,Biada J,Sood S,Rabkin R.Kidney Int.,2010,78(1):89-95
12 Kumar K U,Rao N M,Naidu M P.Int.J.Clin.Surg.,2014,2(4):148-158
13 WANG Zhong-Hua,HE Bing-Shu,SUN Cheng-Long,HE Jiu-Ming,ZHANG Rui-Ping,ABLIZ Zeper.Chinese J.Anal.Chem.,2018,46(3):406-412王中华,何秉淑,孙成龙,宋肖炜,贺玖明,张瑞萍,再帕尔·阿不力孜.分析化学,2018,46(3):406-412
14 Mahmoodpoor F,Rahbar Saadat Y,Barzegari A,Ardalan M,Zununi Vahed S.Biomed.Pharmacother.,2017,93:412-419
15 Wanchai K,Pongchaidecha A,Chatsudthipong V,Chattipakorn S C,Chattipakorn N,Lungkaphin A.Am.J.Med.Sci.,2017,353(1):59-69
16 HU Yong-Sheng,XU Peng-Tao,YE Sheng-Jie,SHI Wen-Yu,GAO Hong-Chang,ZHUO Yang,ZHAO Liang-Cai.Chinese J.Anal.Chem.,2018,46(2):170-177胡永胜,徐鹏涛,叶胜捷,施雯宇,高红昌,卓阳,赵良才.分析化学,2018,46(2):170-177
17 LIU Lai-Lai,DUAN Juan.J.Yunnan Univ.Tradit.Chin.Med.,2013,36(4):93-95刘莱莱,段娟.云南中医学院学报,2013,36(4):93-95
18 Awadh M A,Mohamed K A,Ahmed E A M,Amira A B,Marwa S M D.Saudi J.Biol.Sci.,2015,22(3):302-311
19 Simon C,Elizabeth S.Anaesth.Intensive.Care Med.,2006,7(2):46-48
20 Barrak M P.Clin.Lab.Med.,2015,35(3):487-502
21 Li Z,Lin C,Xu J,Wu H,Feng J,Huang H.Anal.Biochem.,2015,477:105-114
22 Lin C,Wei Z,Cheng K K,Xu J,Shen G,She C,Zhong H,Chang X,Dong J.Sci.Rep.,2017,7(1):6820
23 Ji L L,Miller R H,Nagle F J,Lardy H A,Stratman F W.Metabolism,1987,36(8):748-752
24 Lee C C,Watkins S M,Lorenzo C,Wagenknecht L E,Il'Yasova D,Chen Y I,Haffner S M,Hanley A J.Diabetes Care,2016,39(4):582-588
25 Edmonds M S,Baker D H.J.Anim.Sci.,1987,65(3):699-705
26 Gatnau R,Zimmerman D R,Nissen S L,Wannemuehler M,Ewan R C.J.Anim.Sci.,1995,73(1):159-165
27 Iida A.Nat.Genet.,2005,37(2):138-144
28 WANG Meng,LIU Ming,GUO Lin.Chin.J.Clin.Lab.Sci.,2013,31(6):401-405王萌,刘明,郭健.临床检验杂志,2013,31(6):401-405
29 Klasing K C,Barnes D M.J.Nutr.,1988,118(9):1158-1164
30 Ito T,Yoshikawa N,Inui T,Miyazaki N,Schaffer S W,Azuma J.PLo S One,2014,9(9):e107-e109
31 Mac Lellan D L,Mataija D,Doucette A,Huang W,Langlois C,Trottier G,Burton I W,Walter J A,Karakach T K.Mol.Bio Syst.,2011,7(7):2181-2188
32 Canani R B,Di Costanzo M,Leone L.Clin.Epigenetics,2012,4(1):4
33 Plecko B,Stoeckler-Ipsiroglu S,Schober E,Harrer G,Mlynarik V,Gruber S,Moser E,Moeslinger D,Silgoner H,Ipsiroglu O.Pediatr.Res.,2002,52(2):301-306
34 Kiss Z,Mukherjee J J,Crilly K S,Chung T.Febs J.,2015,250(2):395-402