健康成年人血清中22种胆汁酸亚组分参考区间的建立

Establishment of reference intervals for 22 bile acid subfractions in serum of healthy adults

目的建立健康成年人血清中22种胆汁酸亚组分参考区间。方法收集在首都医科大学附属复兴医院健康管理中心体检的250例表观健康成年人为研究对象,依据美国临床和实验室标准协会(CLSI)C62-A和《液相色谱-质谱临床应用建议》相关标准,使用液相色谱-串联质谱法检测其血清22种胆汁酸亚组分[胆酸(CA)、脱氧胆酸(DCA)、鹅去氧胆酸(CDCA)、猪去氧胆酸(HDCA)、γ-鼠胆酸(γ-MCA)、β-鼠胆酸(β-MCA)、α-鼠胆酸(α-MCA)、熊去氧胆酸(UDCA)、12-酮基石胆酸(12-ketoLCA)、3-脱氢胆酸-1(3-DHCA-1)、石胆酸(LCA)、23-脱甲胆酸(23-Norcholic Acid)、异石胆酸(IsoLCA)、甘氨鹅脱氧胆酸钠盐(GCDCA)、甘氨脱氧胆酸钠盐(GDCA)、甘氨石胆酸(GLCA)、甘氨熊脱氧胆酸(GUDCA)、牛磺胆酸(TCA)、牛磺猪脱氧胆酸钠盐(THDCA)、牛磺脱氧胆酸钠盐(TDCA-1)、牛磺猪胆酸钠盐(THCA-1)、牛磺熊脱氧胆酸二水合物(TDAD-1)]水平,依据CLSI C28-A3建立健康成年人群上述各项的参考区间。结果不同性别健康成年人总胆汁酸及胆汁酸亚组分水平比较,差异无统计学意义(P>0.05)。中青年组与老年组血清THDCA、GDCA、GLCA、γ-MCA、β-MCA、CDCA、HDCA、UDCA、12-ketoLCA、LCA和THCA-1水平比较,差异无统计学意义(P>0.05),故两年龄组可使用统一的参考区间,分别为0.00~65.26、0.59~677.13、0.52~40.21、0.33~81.39、0.00~13.83、5.02~1132.11、0.11~506.99、0.38~682.52、0.02~20.61、0.07~23.88、0.02~8.71 ng/mL。中青年组与老年组血清TCA、TDCA-1、TDAD-1、GUDCA、GCDCA、α-MCA、CA、3-DHCA-1、DCA、23-Norcholic Acid和IsoLCA水平比较,差异有统计学意义(P<0.05),故两年龄组应建立各自的参考区间,中青年组分别为0.51~130.46、0.28~254.25、0.03~50.39、0.92~618.28、29.26~1140.82、0.00~9.55、4.28~538.21、0.02~13.64、0.17~337.80、0.21~25.00、0.03~18.20 ng/mL;老年组分别为0.34~381.20、0.47~658.95、0.02~100.63、1.00~796.97、29.73~1767.08、0.03~48.84、5.05~1226.32、0.07~24.58、0.06~313.06、0.51~125.90、0.08~22.07 ng/mL。结论通过建立健康成年人群胆汁酸亚组分的参考区间,可为后续各种肝胆、胃肠、神经系统疾病的基础研究和临床应用提供参考。

Objective To establish reference intervals for 22 bile acid subfractions in serum of healthy adults.Methods A total of 250 apparently healthy adults who underwent physical examination in the Health Management Center of Fuxing Hospital,Capital Medical University were collected as the research objects.According to America Clinical and Laboratory Standards Institute(CLSI)C62-A and"Recommendations for Clinical Application of Liquid chromatography-Mass spectrometry",the serum levels of 22 bile acid subfractions[cholic acid(CA),deoxycholic acid(DCA),chenodeoxycholic acid(CDCA),hyodeoxycholic acid(HDCA),γ-Murine cholic acid(γ-MCA),β-Murine cholic acid(β-MCA),α-Murine cholic acid(α-MCA),ursodeoxycholic acid(UDCA),12 keto cornerstone cholic acid(12 ketoLCA),3-dehydrocholic acid-1(3-DHCA-1),cholic acid(LCA),23-Norcholic Acid,isocholic acid(IsoLCA),glycine deoxycholate sodium salt(GCDCA),glycine deoxycholate sodium salt(GDCA),glycine cholic acid(GLCA),glycine ursodeoxycholic acid(GUDCA),taurocholic acid(TCA),taurine hyodeoxycholic acid sodium salt(THDCA),taurodeoxycholate sodium salt(TDCA-1),sodium taurocholate(THCA-1),taurodeoxycholate dihydrate(TDAD-1)]were detected by liquid chromatography-tandem mass spectrometry.The reference intervals for the above items in healthy adults were established according to CLSI C28-A3.Results There was no significant difference in total bile acid and bile acid subfractions between healthy adults of different genders(P>0.05).There was no significant difference in serum levels of THDCA,GDCA,GLCA,γ-MCA,β-MCA,CDCA,HDCA,UDCA,12-ketoLCA,LCA and THCA-1 between the young and middle-aged group and the elderly group(P>0.05),therefore,a uniform reference interval could be used for both age groups,the values were 0.00-65.26,0.59-677.13,0.52-40.21,0.33-81.39,0.00-13.83,5.02-1132.11,0.11-506.99,0.38-682.52,0.02-20.61,0.07-23.88,0.02-8.71 ng/mL,respectively.The serum levels of TCA,TDCA-1,TDDAD-1,GUDCA,GCDCA,α-MCA,CA,3-DHCA-1,DCA,23-Norcholic Acid and IsoLCA in the young and middle-aged group were significantly different from those in the elderly group(P<0.05),therefore,the two age groups should establish their own reference intervals,in the young and middle-aged group,the values were 0.51-130.46,0.28-254.25,0.03-50.39,0.92-618.28,29.26-1140.82,0.00-9.55,4.28-538.21,0.02-13.64,0.17-337.80,0.21-25.00,0.03-18.20 ng/mL,respectively,the elderly group were 0.34-381.20,0.47-658.95,0.02-100.63,1.00-796.97,29.73-1767.08,0.03-48.84,5.05-1226.32,0.07-24.58,0.06-313.06,0.51-125.90,0.08-22.07 ng/mL,respectively.Conclusion By establishing the reference intervals of bile acid subfractions in healthy adults population,it can provide reference for the subsequent basic research and clinical application of various hepatobiliary,gastrointestinal and nervous system diseases.