[1]李蓉,曾粒,钟玲.终末期肾脏病血液透析患者血清胆汁酸谱检测与分析[J].第三军医大学学报,2019,41(16):1583-1589.
 LI Rong,ZENG Li,ZHONG Ling.Detection and analysis of serum bile acid profile in patients with end-stage renal disease undergoing hemodialysis[J].J Third Mil Med Univ,2019,41(16):1583-1589.
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终末期肾脏病血液透析患者血清胆汁酸谱检测与分析
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第16期
页码:
1583-1589
栏目:
临床医学
出版日期:
2019-08-30

文章信息/Info

Title:
Detection and analysis of serum bile acid profile in patients with end-stage renal disease undergoing hemodialysis
作者:
李蓉 曾粒 钟玲
重庆医科大学附属第二医院肾内科
Author(s):
 

Department of Nephrology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

关键词:
胆汁酸终末期肾病脂代谢紊乱预后超高效液相色谱-串联质谱
Keywords:
 
分类号:
R446.11;R459.5;R692
文献标志码:
A
摘要:

目的 通过对维持性血液透析患者血清胆汁酸谱的靶向定量检测,探讨终末期肾病(end-stage renal disease,ESRD)胆汁酸谱的变化与代谢并发症及预后的关系。方法 收集2013年12月至2016年12月重庆医科大学附属第二医院77例维持性血液透析患者(ESRD组)及本院体检中心30名健康对照(HC组)的血液标本,采用超高效液相色谱-串联质谱方法对其进行血清胆汁酸的靶向定量检测。结合单变量与多变量统计分析对终末期肾病患者与健康对照进行胆汁酸谱的差异分析。结果检测出6种胆汁酸在组间差异具有统计学意义,其中ESRD组鹅脱氧胆酸、脱氧胆酸、胆酸水平明显降低,甘氨鹅脱氧胆酸、牛磺鹅脱氧胆酸、甘氨胆酸水平明显升高(P<0.05)。亚组分析提示牛磺胆酸、牛磺鹅脱氧胆酸、牛磺猪胆酸、牛磺α鼠胆酸水平在健康对照、终末期肾脏病存活组及死亡组呈逐渐升高趋势,差异具有统计学意义(P<0.01)。结论 终末期肾脏病胆汁酸代谢紊乱与脂代谢异常及不良预后有关。

Abstract:

ObjectiveTo explore the association of serum bile acid profile with metabolic complications and outcomes in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. MethodsBetween December, 2013 and December, 2016, 77 patients with ESRD on maintenance hemodialysis and 30 healthy subjects were recruited from the Second Affiliated Hospital of Chongqing Medical University. Fasting blood samples were collected from all the subjects, and a targeted metabolomics approach based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the changes in serum bile acids between the ESRD patients and the healthy subjects. Univariate and multivariate analyses were performed to screen the differential bile acids between the two groups. ResultsSix differential bile acids were identified as probable biomarkers for differentiation between ESRD patients and healthy subjects. The levels of chenodeoxycholic acid, deoxycholic acid, and cholic acid were significantly decreased, and the levels of glycochenodeoxycholic acid, taurochenodeoxycholic acid, and glycocholic acid were significantly increased in ESRD patients(P<0.05). Subgroup analyses suggested that the levels of taurocholic acid, taurochenodeoxycholic acid, taurohyocholic acid, and tauro α-muricholic acid all increased significantly and progressively in the order of the healthy control group, ESRD survival group, and ESRD death group(P<0.01). ConclusionThe serum bile acid profile of ESRD patients is significantly different from that of healthy subjects, suggesting the association of bile acid metabloism disorder with the occurrence of dyslipidemia and a poor prognosis of ESRD.

参考文献/References:

[1]ZHANG L X, WANG F, WANG L, et al. Prevalence of chronic kidney disease in China: A cross-sectional survey[J]. Lancet, 2012, 379(9818): 815-822. DOI: 10.1016/S0140-6736(12)60033-6.
[2]KATSUMA S, HIRASAWA A, TSUJIMOTO G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1[J]. Biochem Biophys Res Commun, 2005, 329(1): 386-390. DOI: 10.1016/j.bbrc.2005.01.139.
[3]STAYROOK K R, BRAMLETT K S, SAVKUR R S, et al. Regulation of carbohydrate metabolism by the farnesoid X receptor[J]. Endocrinol, 2005, 146(3): 984-991. DOI: 10.1210/en.2004-0965.
[4]HIROKANE H, NAKAHARA M, TACHIBANA S, et al. Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4[J]. J Biol Chem, 2004, 279(44): 45685-45692. DOI: 10.1074/jbc.M404255200.
[5]WATANABE M, HOUTEN S M, WANG L, et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c[J].J Clin Invest, 2004, 113(10): 1408-1418. DOI: 10.1172/JCI21025. 
[6]WATANABE M, HOUTEN S M, MATAKI C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation[J]. Nature, 2006, 439(7075): 484-489. DOI: 10.1038/nature04330.
[7]BALESTRI P L, CUPISTI A. Elevated bile acid serum concentrations in uremics[J]. Nephron, 1996, 72(2): 325. DOI: 10.1159/000188867.
[8]YU H Y, NI Y, BAO Y Q, et al. Chenodeoxycholic acid as a potential prognostic marker for roux-En-Y gastric bypass in Chinese obese patients[J]. J Clin Endocrinol Metab, 2015, 100(11): 4222-4230. DOI: 10.1210/jc.2015-2884. 
[9]JIMENEZ F, MONTE M J, EL-MIR M Y, et al. Chronic renal failure-induced changes in serum and urine bile acid profiles[J]. Dig Dis Sci, 2002, 47(11): 2398-2406.
[10]CHU L, ZHANG K K, ZHANG Y Y, et al. Mechanism underlying an elevated serum bile acid level in chronic renal failure patients[J]. Int Urol Nephrol, 2015, 47(2): 345-351. DOI: 10.1007/s11255-014-0901-0.
[11]GAI Z B, CHU L, HILLER C, et al. Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters[J]. Am J Physiol Renal Physiol, 2014, 306(1): F130-F137. DOI: 10.1152/ajprenal.00114.2013.
[12]LEFEBVRE P, CARIOU B, LIEN F, et al. Role of bile acids and bile acid receptors in metabolic regulation[J]. Physiol Rev, 2009, 89(1): 147-191. DOI: 10.1152/physrev.00010.2008.
[13]JIA W, XIE G X, JIA W P. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(2): 111-128. DOI: 10.1038/nrgastro.2017.119.
[14]SONG P Z, ROCKWELL C E, CUI J Y, et al. Individual bile acids have differential effects on bile acid signaling in mice[J]. Toxicol Appl Pharmacol, 2015, 283(1): 57-64. DOI: 10.1016/j.taap.2014.12.005.
[15]VAQUERO J, MONTE M J, DOMINGUEZ M, et al. Differential activation of the human farnesoid X receptor depends on the pattern of expressed isoforms and the bile acid pool composition[J]. Biochem Pharmacol, 2013, 86(7): 926-939. DOI: 10.1016/j.bcp.2013.07.022.
[16]CARULLI N, PONZ DE LEON M, PODDA M, et al. Chenodeoxycholic acid and ursodeoxycholic acid effects in endogenous hypertriglyceridemias. A controlled double-blind trial[J]. J Clin Pharmacol, 1981, 21(10): 436-442.
[17]SIRVENT A, CLAUDEL T, MARTIN G, et al. The farnesoid X receptor induces very low density lipoprotein receptor gene expression[J]. FEBS Lett, 2004, 566(1/2/3): 173-177. DOI: 10.1016/j.febslet.2004.04.026.
[18]KALANTAR-ZADEH K, BLOCK G, HUMPHREYS M H, et al. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients[J]. Kidney Int, 2003, 63(3): 793-808. DOI: 10.1046/j.1523-1755.2003.00803.x.
[19]NILSSON L M, ABRAHAMSSON A, SAHLIN S, et al. Bile acids and lipoprotein metabolism: effects of cholestyramine and chenodeoxycholic acid on human hepatic mRNA expression[J]. Biochem Biophys Res Commun, 2007, 357(3): 707-711. DOI: 10.1016/j.bbrc.2007.03.196.
[20]LEVY M, THAISS C A, ZEEVI D, et al. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling[J]. Cell, 2015, 163(6): 1428-1443. DOI: 10.1016/j.cell.2015.10.048.
 

更新日期/Last Update: 2019-08-22