Hepatic encephalopathy (HE), a neurological disease resulting from liver failure, is difficult to manage and its causes are unclear. Bile acids have been postulated to be involved in the provenance and progression of various diseases including HE. Hence, the characterization of bile acid profiles in the brains of subjects with and without liver failure can provide important clues for the potential treatment of HE. Nanoflow ultra‐performance liquid chromatography electrospray ionization ion mobility mass spectrometry (UPLC‐ESI‐IM‐MS) is a highly sensitive method for detection of specific molecules, such as bile acids in brain samples, at biologically relevant concentrations. We used UPLC‐ESI‐IM‐MS to characterize bile acid profiles in brain samples from seven “healthy” control rodents and 22 “diseased” rodents with liver failure (i.e., induced HE). An isomer of trihydroxycholanoyl‐taurine was detected in brain tissue samples from both rats and mice with induced HE; however, this isomer was not detected in the brains of healthy rats and mice. Our findings were confirmed by comparing IM arrival times (AT), exact mass measurements (m/z), and mass spectral fragmentation patterns of the experimentally observed suspected species to standards of trihydroxycholanoyl‐taurine isomers. Moreover, In Silico Fractionation was employed to provide an additional analytical dimension to verify bile acid identifications.

中文翻译：

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肝性脑病啮齿动物脑中的三羟基胆酰牛磺酸

肝性脑病 (HE) 是一种由肝功能衰竭引起的神经系统疾病，难以治疗，其原因尚不清楚。据推测，胆汁酸与包括 HE 在内的各种疾病的起源和进展有关。因此，有和没有肝功能衰竭受试者大脑中胆汁酸谱的特征可以为 HE 的潜在治疗提供重要线索。纳流超高效液相色谱电喷雾电离离子迁移质谱 (UPLC-ESI-IM-MS) 是一种高度灵敏的方法，用于检测特定分子，例如脑样本中的胆汁酸，其浓度与生物相关。我们使用 UPLC-ESI-IM-MS 来表征来自 7 只“健康”对照啮齿动物和 22 只患有肝功能衰竭（即诱导 HE）的“患病”啮齿动物的脑样本中的胆汁酸谱。在诱发 HE 的大鼠和小鼠的脑组织样本中检测到三羟基胆酰基牛磺酸的异构体；然而，在健康大鼠和小鼠的大脑中没有检测到这种异构体。我们的发现通过比较 IM 到达时间 (AT)、精确质量测量值 (m/z )，以及实验观察到的可疑物种的质谱碎片模式，符合三羟基胆酰基-牛磺酸异构体的标准。此外，硅胶分馏用于提供额外的分析维度来验证胆汁酸的鉴定。