Nephrology Department of Guilin No. 924 Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin Key Laboratory of Kidney Diseases Research, Guilin, Guangxi, China (mainland).
Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China (mainland).
Ann Transplant. 2020 Jun 23;25:e921844. doi: 10.12659/AOT.921844.
BACKGROUND There are many situations of abnormal metabolism influencing liver graft function. This study aims to provide data for the development of liver function recovery after liver transplantation by dynamically analyzing metabolites of bile acids pathway in serum. MATERIAL AND METHODS A comprehensive metabolomics profiling of serum of 9 liver transplantation patients before transplantation, on the 1st, 3rd, and 7th days after liver transplantation, and healthy individuals were performed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Multivariate data and dynamic analysis were used to search for biomarkers between the metabolomics profiles present in perioperative liver transplantation and normal controls. RESULTS Thirty-three differential endogenous metabolites were screened by the threshold of variable importance in the projection (VIP) from an orthogonal partial least square discriminant analysis (OPLS-DA) greater than 1.0, q-value <0.05, and fold change (FC) ≤0.8 or ≥1.2 between the preoperative group and the normal controls in negative mode. The metabolite intensities of taurocholic acid, taurochenodeoxycholic acid, chenodeoxycholic acid glycine conjugate, and glycocholic acid pre-transplantation were significantly higher than those of normal controls. The average metabolite intensities of taurocholic acid and taurochenodesoxycholic acid on the first day after liver transplantation were lower than those observed pre-transplantation. The average metabolite intensities on day 3 after liver transplantation showed a sudden increase and then decreased after 7 postoperative days. The average metabolite intensities of glycocholic acid and chenodeoxycholic acid glycine conjugate showed an increasing trend on the 1st, 3rd, and 7th days after liver transplantation. CONCLUSIONS Use of taurocholic acid and taurochenodeoxycholic acid-related bile secretion, liver regeneration, and de novo bile acid synthesis may help clinical evaluation and provide data for the development of liver function recovery after liver transplantation.
有许多影响肝移植物功能的异常代谢情况。本研究旨在通过动态分析血清胆汁酸途径代谢物,为肝移植后肝功能恢复提供数据。
采用超高效液相色谱-质谱联用(UPLC-MS)对 9 例肝移植患者术前、术后第 1、3、7 天及健康对照者的血清进行全面代谢组学分析。采用多元数据分析和动态分析方法,寻找围手术期肝移植与正常对照组之间存在的代谢组学特征的生物标志物。
通过正交偏最小二乘判别分析(OPLS-DA)筛选出 VIP 值大于 1.0、q 值<0.05、FC 值≤0.8 或≥1.2 的 33 个差异内源性代谢物。在负模式下,术前组与正常对照组相比,牛磺胆酸、牛磺鹅脱氧胆酸、鹅脱氧胆酸甘氨酸结合物和甘氨胆酸的代谢物强度明显升高。移植前,牛磺胆酸和牛磺鹅脱氧胆酸的平均代谢物强度均明显高于正常对照组。肝移植后第 1 天,牛磺胆酸和牛磺鹅脱氧胆酸的平均代谢物强度低于移植前。术后第 3 天,平均代谢物强度突然升高,术后第 7 天降低。移植后第 1、3、7 天,甘氨胆酸和鹅脱氧胆酸甘氨酸结合物的平均代谢物强度呈上升趋势。
利用牛磺胆酸和牛磺鹅脱氧胆酸相关的胆汁分泌、肝脏再生和从头合成胆汁酸可能有助于临床评估,并为肝移植后肝功能恢复提供数据。