University of Manitoba, Winnipeg, Manitoba, Canada.
University of Winnipeg, Winnipeg, Manitoba, Canada.
NMR Biomed. 2019 May;32(5):e4065. doi: 10.1002/nbm.4065. Epub 2019 Feb 8.
Primary sclerosing cholangitis (PSC) has been considered to be either an "autoimmune disease" or a "bile acid-induced injury." In vitro MRS studies on PSC patients have limitations due to the contamination of bile with contrast agent (commonly administered during endoscopic retrograde cholangiopancreatography) and/or the use of patient cohorts with other diseases as controls. The objective of this study was to quantify biliary metabolites using in vivo H MRS and gain insight into the pathogenesis of PSC. Biliary metabolites in 10 PSC patients and 14 healthy controls were quantified in vivo using H MRS on a 3 T MR scanner. The concentrations of total bile acids plus cholesterol, glycine-conjugated bile acids, taurine-conjugated bile acids, and choline-containing phospholipids (chol-PLs) were compared between the two groups. There were statistically significant decreases in the levels of the above mentioned biliary metabolites in the PSC patients compared with controls. The reduction in bile acid secretion in bile of PSC patients indicates accumulation of bile acids in hepatocytes. Moreover, reduction in the levels of chol-PLs in bile may increase the toxic effects of bile acids. Our findings suggest that the bile duct injury in PSC patients is most likely due to "bile acid-induced injury."
原发性硬化性胆管炎(PSC)被认为是一种“自身免疫性疾病”或“胆汁酸诱导损伤”。由于胆汁中存在对比剂(通常在经内镜逆行胰胆管造影术期间给予)的污染和/或使用患有其他疾病的患者队列作为对照,PSC 患者的 MRS 体外研究存在局限性。本研究的目的是使用体内 H MRS 定量胆汁代谢物,并深入了解 PSC 的发病机制。使用 3T MR 扫描仪对 10 名 PSC 患者和 14 名健康对照者进行体内 H MRS 以定量胆汁代谢物。比较两组之间总胆汁酸加胆固醇、甘氨酸结合胆汁酸、牛磺酸结合胆汁酸和含有胆碱的磷脂(胆-PL)的浓度。与对照组相比,PSC 患者的上述胆汁代谢物水平显著降低。PSC 患者胆汁中胆汁酸分泌减少表明胆汁酸在肝细胞中蓄积。此外,胆汁中胆-PL 水平的降低可能会增加胆汁酸的毒性作用。我们的发现表明,PSC 患者的胆管损伤很可能是由于“胆汁酸诱导损伤”。